Skip to main content
SpringerLink
Log in

Fatty Acid Mediators in the Tumor Microenvironment

  • Chapter
  • First Online:
Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1259))

Abstract

Patients with cancer frequently overexpress inflammatory cytokines with an associated neutrophilia both of which may be downregulated by diets with high omega-3 polyunsaturated fatty acids (ω-3 PUFA). The anti-inflammatory activity of dietary ω-3 PUFA has been suggested to have anticancer properties and to improve survival of cancer patients. Currently, the majority of dietary research efforts do not differentiate between obesity and dietary fatty acid consumption as mediators of inflammatory cell expansion and tumor microenvironmental infiltration, initiation, and progression. In this chapter, we discuss the relationships between dietary lipids, inflammation, neoplasia and strategies to regulate these relationships. We posit that dietary composition, notably the ratio of ω-3 vs. ω-6 PUFA, regulates tumor initiation and progression and the frequency and sites of metastasis that, together, impact overall survival (OS). We focus on three broad topics: first, the role of dietary lipids in chronic inflammation and tumor initiation, progression, and regression; second, lipid mediators linking inflammation and cancer; and third, dietary lipid regulation of murine and human tumor initiation, progression, and metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, Wang YY, Meulle A, Salles B, Le Gonidec S, Garrido I, Escourrou G, Valet P, Muller C (2011) Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res 71:2455–2465

    Article  CAS  PubMed  Google Scholar 

  2. Andarawewa KL, Motrescu ER, Chenard MP, Gansmuller A, Stoll I, Tomasetto C, Rio MC (2005) Stromelysin-3 is a potent negative regulator of adipogenesis participating to cancer cell-adipocyte interaction/crosstalk at the tumor invasive front. Cancer Res 65:10862–10871

    Article  CAS  PubMed  Google Scholar 

  3. Arendt LM, McCready J, Keller PJ, Baker DD, Naber SP, Seewaldt V, Kuperwasser C (2013) Obesity promotes breast cancer by CCL2-mediated macrophage recruitment and angiogenesis. Cancer Res 73:6080–6093

    Article  CAS  PubMed  Google Scholar 

  4. Zeyda M, Stulnig TM (2007) Adipose tissue macrophages. Immunol Lett 112:61–67

    Article  CAS  PubMed  Google Scholar 

  5. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sartipy P, Loskutoff DJ (2003) Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A 100:7265–7270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rogers NH, Perfield JW 2nd, Strissel KJ, Obin MS, Greenberg AS (2009) Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology 150:2161–2168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nishimoto S, Fukuda D, Higashikuni Y, Tanaka K, Hirata Y, Murata C, Kim-Kaneyama JR, Sato F, Bando M, Yagi S, Soeki T, Hayashi T, Imoto I, Sakaue H, Shimabukuro M, Sata M (2016) Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance. Sci Adv 2:e1501332

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Wall R, Ross RP, Fitzgerald GF, Stanton C (2010) Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 68:280–289

    Article  PubMed  Google Scholar 

  10. Serhan CN (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 25:101–137

    Article  CAS  PubMed  Google Scholar 

  11. Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8:349–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mocellin MC, Camargo CQ, Nunes EA, Fiates GM, Trindade EB (2016) A systematic review and meta-analysis of the n-3 polyunsaturated fatty acids effects on inflammatory markers in colorectal cancer. Clin Nutr 35:359–369

    Article  CAS  PubMed  Google Scholar 

  13. Badwey JA, Curnutte JT, Robinson JM, Berde CB, Karnovsky MJ, Karnovsky ML (1984) Effects of free fatty acids on release of superoxide and on change of shape by human neutrophils. Reversibility by albumin. J Biol Chem 259:7870–7877

    Article  CAS  PubMed  Google Scholar 

  14. Bates EJ, Ferrante A, Smithers L, Poulos A, Robinson BS (1995) Effect of fatty acid structure on neutrophil adhesion, degranulation and damage to endothelial cells. Atherosclerosis 116:247–259

    Article  CAS  PubMed  Google Scholar 

  15. Soyland E, Nenseter MS, Braathen L, Drevon CA (1993) Very long chain n-3 and n-6 polyunsaturated fatty acids inhibit proliferation of human T-lymphocytes in vitro. Eur J Clin Investig 23:112–121

    Article  CAS  Google Scholar 

  16. Santoli D, Phillips PD, Colt TL, Zurier RB (1990) Suppression of interleukin 2-dependent human T cell growth in vitro by prostaglandin E (PGE) and their precursor fatty acids. Evidence for a PGE-independent mechanism of inhibition by the fatty acids. J Clin Invest 85:424–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kelly JP, Parker CW (1979) Effects of arachidonic acid and other unsaturated fatty acids on mitogenesis in human lymphocytes. J Immunol 122:1556–1562

    CAS  PubMed  Google Scholar 

  18. Calder PC (1998) Dietary fatty acids and the immune system. Nutr Rev 56:S70–S83

    Article  CAS  PubMed  Google Scholar 

  19. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC et al (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 320:265–271

    Article  CAS  PubMed  Google Scholar 

  20. German JB, Lokesh B, Kinsella JE (1988) The effect of dietary fish oils on eicosanoid biosynthesis in peritoneal macrophages is influenced by both dietary N-6 polyunsaturated fats and total dietary fat. Prostaglandins Leukot Essent Fatty Acids 34:37–45

    Article  CAS  PubMed  Google Scholar 

  21. Siriwardhana N, Kalupahana NS, Fletcher S, Xin W, Claycombe KJ, Quignard-Boulange A, Zhao L, Saxton AM (2012) Moustaid-Moussa N: n-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via NF-kappaB-dependent mechanisms. J Nutr Biochem 23:1661–1667

    Article  CAS  PubMed  Google Scholar 

  22. Babu US, Bunning VK, Wiesenfeld P, Raybourne RB, O’Donnell M (1997) Effect of dietary flaxseed on fatty acid composition, superoxide, nitric oxide generation and antilisterial activity of peritoneal macrophages from female Sprague-Dawley rats. Life Sci 60:545–554

    Article  CAS  PubMed  Google Scholar 

  23. Turek JJ, Schoenlein IA, Bottoms GD (1991) The effect of dietary n-3 and n-6 fatty acids on tumor necrosis factor-alpha production and leucine aminopeptidase levels in rat peritoneal macrophages. Prostaglandins Leukot Essent Fatty Acids 43:141–149

    Article  CAS  PubMed  Google Scholar 

  24. Jeffery NM, Newsholme EA, Calder PC (1997) Level of polyunsaturated fatty acids and the n-6 to n-3 polyunsaturated fatty acid ratio in the rat diet alter serum lipid levels and lymphocyte functions. Prostaglandins Leukot Essent Fatty Acids 57:149–160

    Article  CAS  PubMed  Google Scholar 

  25. Turchini GM, Nichols PD, Barrow C, Sinclair AJ (2012) Jumping on the omega-3 bandwagon: distinguishing the role of long-chain and short-chain omega-3 fatty acids. Crit Rev Food Sci Nutr 52:795–803

    Article  CAS  PubMed  Google Scholar 

  26. Simopoulos AP (2002) Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 21:495–505

    Article  CAS  PubMed  Google Scholar 

  27. Wild GE, Drozdowski L, Tartaglia C, Clandinin MT, Thomson AB (2007) Nutritional modulation of the inflammatory response in inflammatory bowel disease--from the molecular to the integrative to the clinical. World J Gastroenterol 13:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. James M, Proudman S, Cleland L (2010) Fish oil and rheumatoid arthritis: past, present and future. Proc Nutr Soc 69:316–323

    Article  CAS  PubMed  Google Scholar 

  29. Pasqualini R, Arap W, McDonald DM (2002) Probing the structural and molecular diversity of tumor vasculature. Trends Mol Med 8:563–571

    Article  CAS  PubMed  Google Scholar 

  30. Minami Y, Sasaki T, Kawabe J I, Ohsaki Y (2013) Accessory cells in tumor angiogenesis—tumor–associated pericytes. In: Research directions in tumor angiogenesis. (London: InTechOpen Limited), London, pp 73–88

    Google Scholar 

  31. Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM (2002) Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol 160:985–1000

    Article  PubMed  PubMed Central  Google Scholar 

  32. O’Keeffe MB, Devlin AH, Burns AJ, Gardiner TA, Logan ID, Hirst DG, McKeown SR (2008) Investigation of pericytes, hypoxia, and vascularity in bladder tumors: association with clinical outcomes. Oncol Res 17:93–101

    Article  PubMed  Google Scholar 

  33. Stefansson IM, Salvesen HB, Akslen LA (2006) Vascular proliferation is important for clinical progress of endometrial cancer. Cancer Res 66:3303–3309

    Article  CAS  PubMed  Google Scholar 

  34. Yonenaga Y, Mori A, Onodera H, Yasuda S, Oe H, Fujimoto A, Tachibana T, Imamura M (2005) Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients. Oncology 69:159–166

    Article  PubMed  Google Scholar 

  35. Xian X, Hakansson J, Stahlberg A, Lindblom P, Betsholtz C, Gerhardt H, Semb H (2006) Pericytes limit tumor cell metastasis. J Clin Invest 116:642–651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Turner EC, Mulvaney EP, Reid HM, Kinsella BT (2011) Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK1: role in endothelial cell migration and angiogenesis. Mol Biol Cell 22:2664–2679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhu W, Saddar S, Seetharam D, Chambliss KL, Longoria C, Silver DL, Yuhanna IS, Shaul PW, Mineo C (2008) The scavenger receptor class B type I adaptor protein PDZK1 maintains endothelial monolayer integrity. Circ Res 102:480–487

    Article  CAS  PubMed  Google Scholar 

  38. Honn KV, Cicone B, Skoff A (1981) Prostacyclin: a potent antimetastatic agent. Science 212:1270–1272

    Article  CAS  PubMed  Google Scholar 

  39. Minami Y, Sasaki T, Bochimoto H, Kawabe J, Endo S, Hira Y, Watanabe T, Okumura S, Hasebe N, Ohsaki Y (2015) Prostaglandin I2 analog suppresses lung metastasis by recruiting pericytes in tumor angiogenesis. Int J Oncol 46:548–554

    Article  PubMed  CAS  Google Scholar 

  40. DeCaterina R, Giannessi D, Mazzone A, Bernini W, Lazzerini G, Maffei S, Cerri M, Salvatore L, Weksler B (1990) Vascular prostacyclin is increased in patients ingesting omega-3 polyunsaturated fatty acids before coronary artery bypass graft surgery. Circulation 82:428–438

    Article  CAS  PubMed  Google Scholar 

  41. Malyguine A, Umansky V, Shurin MR (2013) Role of the immunological environment in cancer initiation, development and progression. In: Shurin MR, Umansky V, Malyguine A (eds) The tumor immunoenvironment. Springer, Dordrecht, pp 1–12

    Google Scholar 

  42. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545

    Article  CAS  PubMed  Google Scholar 

  43. Mueller MM, Fusenig NE (2004) Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4:839–849

    Article  CAS  PubMed  Google Scholar 

  44. Hussain SP, Harris CC (2007) Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 121:2373–2380

    Article  CAS  PubMed  Google Scholar 

  45. Jackson L, Evers BM (2006) Chronic inflammation and pathogenesis of GI and pancreatic cancers. Cancer Treat Res 130:39–65

    Article  CAS  PubMed  Google Scholar 

  46. Schottenfeld D, Beebe-Dimmer J (2006) Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin 56:69–83

    Article  PubMed  Google Scholar 

  47. Itzkowitz SH, Yio X (2004) Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 287:G7–17

    Google Scholar 

  48. Nelson WG, De Marzo AM, DeWeese TL, Isaacs WB (2004) The role of inflammation in the pathogenesis of prostate cancer. J Urol 172:S6–11; discussion S-2

    Google Scholar 

  49. O’Byrne KJ, Dalgleish AG (2001) Chronic immune activation and inflammation as the cause of malignancy. Br J Cancer 85:473–483

    Article  PubMed  PubMed Central  Google Scholar 

  50. Whitcomb DC (2004) Inflammation and cancer V. Chronic pancreatitis and pancreatic cancer. Am J Physiol Gastrointest Liver Physiol 287:G315–G319

    Article  CAS  PubMed  Google Scholar 

  51. Matsuzaki K, Murata M, Yoshida K, Sekimoto G, Uemura Y, Sakaida N, Kaibori M, Kamiyama Y, Nishizawa M, Fujisawa J, Okazaki K, Seki T (2007) Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor beta signaling, promoting cirrhosis and hepatocellular carcinoma. Hepatology 46:48–57

    Article  CAS  PubMed  Google Scholar 

  52. Philpott M, Ferguson LR (2004) Immunonutrition and cancer. Mutat Res 551:29–42

    Article  CAS  PubMed  Google Scholar 

  53. Herszenyi L, Miheller P, Tulassay Z (2007) Carcinogenesis in inflammatory bowel disease. Dig Dis 25:267–269

    Article  PubMed  Google Scholar 

  54. Seril DN, Liao J, Yang GY, Yang CS (2003) Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. Carcinogenesis 24:353–362

    Article  CAS  PubMed  Google Scholar 

  55. Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J (2000) Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment Pharmacol Ther 14:145–153

    Article  CAS  PubMed  Google Scholar 

  56. Halliday GM (2005) Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis. Mutat Res 571:107–120

    Article  CAS  PubMed  Google Scholar 

  57. Thorn RM, Fisher MS, Kripke ML (1981) Further characterization of immunological unresponsiveness induced in mice by ultraviolet radiation. II. Studies on the origin and activity of ultraviolet-induced suppressor lymphocytes. Transplantation 31:129–133

    Article  CAS  PubMed  Google Scholar 

  58. Rajalingam K, Schreck R, Rapp UR, Albert S (1773) Ras oncogenes and their downstream targets. Biochim Biophys Acta 2007:1177–1195

    Google Scholar 

  59. Strano S, Dell’Orso S, Di Agostino S, Fontemaggi G, Sacchi A, Blandino G (2007) Mutant p53: an oncogenic transcription factor. Oncogene 26:2212–2219

    Article  CAS  PubMed  Google Scholar 

  60. Hattori Y, Nishigori C, Tanaka T, Uchida K, Nikaido O, Osawa T, Hiai H, Imamura S, Toyokuni S (1996) 8-hydroxy-2′-deoxyguanosine is increased in epidermal cells of hairless mice after chronic ultraviolet B exposure. J Invest Dermatol 107:733–737

    Article  CAS  PubMed  Google Scholar 

  61. Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17:1195–1214

    Article  CAS  PubMed  Google Scholar 

  62. Marnett LJ (2000) Oxyradicals and DNA damage. Carcinogenesis 21:361–370

    Article  CAS  PubMed  Google Scholar 

  63. Jaiswal M, LaRusso NF, Burgart LJ, Gores GJ (2000) Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res 60:184–190

    CAS  PubMed  Google Scholar 

  64. Hoki Y, Hiraku Y, Ma N, Murata M, Matsumine A, Nagahama M, Shintani K, Uchida A, Kawanishi S (2007) iNOS-dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis. Cancer Sci 98:163–168

    Article  CAS  PubMed  Google Scholar 

  65. Xu H, Chaturvedi R, Cheng Y, Bussiere FI, Asim M, Yao MD, Potosky D, Meltzer SJ, Rhee JG, Kim SS, Moss SF, Hacker A, Wang Y, Casero RA Jr, Wilson KT (2004) Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis. Cancer Res 64:8521–8525

    Article  CAS  PubMed  Google Scholar 

  66. Babbar N, Casero RA Jr (2006) Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: a potential mechanism for inflammation-induced carcinogenesis. Cancer Res 66:11125–11130

    Article  CAS  PubMed  Google Scholar 

  67. Ohshima H, Sawa T, Akaike T (2006) 8-nitroguanine, a product of nitrative DNA damage caused by reactive nitrogen species: formation, occurrence, and implications in inflammation and carcinogenesis. Antioxid Redox Signal 8:1033–1045

    Article  CAS  PubMed  Google Scholar 

  68. Yermilov V, Rubio J, Becchi M, Friesen MD, Pignatelli B, Ohshima H (1995) Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro. Carcinogenesis 16:2045–2050

    Article  CAS  PubMed  Google Scholar 

  69. Kawanishi S, Hiraku Y (2006) Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation. Antioxid Redox Signal 8:1047–1058

    Article  CAS  PubMed  Google Scholar 

  70. Pinlaor S, Sripa B, Ma N, Hiraku Y, Yongvanit P, Wongkham S, Pairojkul C, Bhudhisawasdi V, Oikawa S, Murata M, Semba R, Kawanishi S (2005) Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion. World J Gastroenterol 11:4644–4649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bartsch H, Nair J (2005) Accumulation of lipid peroxidation-derived DNA lesions: potential lead markers for chemoprevention of inflammation-driven malignancies. Mutat Res 591:34–44

    Article  CAS  PubMed  Google Scholar 

  72. Ying L, Hofseth AB, Browning DD, Nagarkatti M, Nagarkatti PS, Hofseth LJ (2007) Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation. Cancer Res 67:9286–9293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Hofseth LJ, Saito S, Hussain SP, Espey MG, Miranda KM, Araki Y, Jhappan C, Higashimoto Y, He P, Linke SP, Quezado MM, Zurer I, Rotter V, Wink DA, Appella E, Harris CC (2003) Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc Natl Acad Sci U S A 100:143–148

    Article  CAS  PubMed  Google Scholar 

  74. Kroncke KD (2003) Nitrosative stress and transcription. Biol Chem 384:1365–1377

    Article  PubMed  Google Scholar 

  75. Cerutti PA, Trump BF (1991) Inflammation and oxidative stress in carcinogenesis. Cancer cells (Cold Spring Harbor, NY: 1989) 3:1–7

    CAS  Google Scholar 

  76. Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4:E131–E136

    Article  CAS  PubMed  Google Scholar 

  77. Odegaard JI, Chawla A (2011) Alternative macrophage activation and metabolism. Annu Rev Pathol 6:275–297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA, Greaves DR, Murray PJ, Chawla A (2006) Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab 4:13–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Huang SC, Everts B, Ivanova Y, O’Sullivan D, Nascimento M, Smith AM, Beatty W, Love-Gregory L, Lam WY, O’Neill CM, Yan C, Du H, Abumrad NA, Urban JF Jr, Artyomov MN, Pearce EL, Pearce EJ (2014) Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol 15:846–855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, Ellenson LH, Caputo T, Lee AH, Conejo-Garcia JR, Glimcher LH (2015) ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell 161:1527–1538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Herber DL, Cao W, Nefedova Y, Novitskiy SV, Nagaraj S, Tyurin VA, Corzo A, Cho HI, Celis E, Lennox B, Knight SC, Padhya T, McCaffrey TV, McCaffrey JC, Antonia S, Fishman M, Ferris RL, Kagan VE, Gabrilovich DI (2010) Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med 16:880–886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ramakrishnan R, Tyurin VA, Veglia F, Condamine T, Amoscato A, Mohammadyani D, Johnson JJ, Zhang LM, Klein-Seetharaman J, Celis E, Kagan VE, Gabrilovich DI (2014) Oxidized lipids block antigen cross-presentation by dendritic cells in cancer. J Immunol 192:2920–2931

    Article  PubMed  CAS  Google Scholar 

  83. Al-Khami AA, Rodriguez PC, Ochoa AC (2017) Energy metabolic pathways control the fate and function of myeloid immune cells. J Leukoc Biol 102:369–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Buck MD, Sowell RT, Kaech SM, Pearce EL (2017) Metabolic instruction of immunity. Cell 169:570–586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Al-Khami AA, Rodriguez PC, Ochoa AC (2016) Metabolic reprogramming of myeloid-derived suppressor cells (MDSC) in cancer. Onco Targets Ther 5:e1200771

    Google Scholar 

  86. Hossain F, Al-Khami AA, Wyczechowska D, Hernandez C, Zheng L, Reiss K, Valle LD, Trillo-Tinoco J, Maj T, Zou W, Rodriguez PC, Ochoa AC (2015) Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res 3:1236–1247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Al-Khami AA, Zheng L, Del Valle L, Hossain F, Wyczechowska D, Zabaleta J, Sanchez MD, Dean MJ, Rodriguez PC, Ochoa AC (2017) Exogenous lipid uptake induces metabolic and functional reprogramming of tumor-associated myeloid-derived suppressor cells. Onco Targets Ther 6:e1344804

    Google Scholar 

  88. Condamine T, Dominguez GA, Youn JI, Kossenkov AV, Mony S, Alicea-Torres K, Tcyganov E, Hashimoto A, Nefedova Y, Lin C, Partlova S, Garfall A, Vogl DT, Xu X, Knight SC, Malietzis G, Lee GH, Eruslanov E, Albelda SM, Wang X, Mehta JL, Bewtra M, Rustgi A, Hockstein N, Witt R, Masters G, Nam B, Smirnov D, Sepulveda MA, Gabrilovich DI (2016) Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 1(2):aaf8943

    Google Scholar 

  89. Sieow JL, Gun SY, Wong SC (2018) The sweet surrender: how myeloid cell metabolic plasticity shapes the tumor microenvironment. Front Cell Dev Biol 6:168

    Article  PubMed  PubMed Central  Google Scholar 

  90. Yan D, Adeshakin AO, Xu M, Afolabi LO, Zhang G, Chen YH, Wan X (2019) Lipid metabolic pathways confer the immunosuppressive function of myeloid-derived suppressor cells in tumor. Front Immunol 10:1399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Consonni FM, Porta C, Marino A, Pandolfo C, Mola S, Bleve A, Sica A (2019) Myeloid-derived suppressor cells: ductile targets in disease. Front Immunol 10:949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Veglia F, Tyurin V, Kagan V, Gabrilovich D (2015) Abstract 467: Oxidized lipids contribute to the suppression function of myeloid derived suppressor cells in cancer. Cancer Res 75:467

    Google Scholar 

  93. Cao W, Gabrilovich D (2011) Abstract 3649: Contribution of fatty acid accumulation to myeloid-derived suppressor cell function in cancer. Cancer Res 71:3649

    Article  CAS  Google Scholar 

  94. Veglia F, Tyurin VA, Kagan VE, Gabrilovich D (2018) Abstract 5133: Lipids and suppressive functions of MDSC in cancer. Cancer Res 78:5133

    Google Scholar 

  95. Laisupasin P, Thompat W, Sukarayodhin S, Sornprom A, Sudjaroen Y (2013) Comparison of serum lipid profiles between normal controls and breast cancer patients. J Lab Phys 5:38–41

    CAS  Google Scholar 

  96. Delimaris I, Faviou E, Antonakos G, Stathopoulou E, Zachari A, Dionyssiou-Asteriou A (2007) Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer. Clin Biochem 40:1129–1134

    Article  CAS  PubMed  Google Scholar 

  97. Fiorenza AM, Branchi A, Sommariva D (2000) Serum lipoprotein profile in patients with cancer. A comparison with non-cancer subjects. Int J Clin Lab Res 30:141–145

    Article  CAS  PubMed  Google Scholar 

  98. Freigang S, Ampenberger F, Weiss A, Kanneganti TD, Iwakura Y, Hersberger M, Kopf M (2013) Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1alpha and sterile vascular inflammation in atherosclerosis. Nat Immunol 14:1045–1053

    Article  CAS  PubMed  Google Scholar 

  99. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC (2011) Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 186:3299–3303

    Article  CAS  PubMed  Google Scholar 

  100. Robblee MM, Kim CC, Porter Abate J, Valdearcos M, Sandlund KL, Shenoy MK, Volmer R, Iwawaki T, Koliwad SK (2016) Saturated fatty acids engage an IRE1alpha-dependent pathway to activate the NLRP3 inflammasome in myeloid cells. Cell Rep 14:2611–2623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Hale JS, Otvos B, Sinyuk M, Alvarado AG, Hitomi M, Stoltz K, Wu Q, Flavahan W, Levison B, Johansen ML, Schmitt D, Neltner JM, Huang P, Ren B, Sloan AE, Silverstein RL, Gladson CL, DiDonato JA, Brown JM, McIntyre T, Hazen SL, Horbinski C, Rich JN, Lathia JD (2014) Cancer stem cell-specific scavenger receptor CD36 drives glioblastoma progression. Stem Cells 32:1746–1758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Incio J, Liu H, Suboj P, Chin SM, Chen IX, Pinter M, Ng MR, Nia HT, Grahovac J, Kao S, Babykutty S, Huang Y, Jung K, Rahbari NN, Han X, Chauhan VP, Martin JD, Kahn J, Huang P, Desphande V, Michaelson J, Michelakos TP, Ferrone CR, Soares R, Boucher Y, Fukumura D, Jain RK (2016) Obesity-induced inflammation and desmoplasia promote pancreatic cancer progression and resistance to chemotherapy. Cancer Discov 6:852–869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Worm SW, Kamara DA, Reiss P, Kirk O, El-Sadr W, Fux C, Fontas E, Phillips A, D’Arminio Monforte A, De Wit S, Petoumenos K, Friis-Mller N, Mercie P, Lundgren JD, Sabin C (2011) Elevated triglycerides and risk of myocardial infarction in HIV-positive persons. AIDS 25:1497–1504

    Article  CAS  PubMed  Google Scholar 

  104. Balaban S, Shearer RF, Lee LS, van Geldermalsen M, Schreuder M, Shtein HC, Cairns R, Thomas KC, Fazakerley DJ, Grewal T, Holst J, Saunders DN, Hoy AJ (2017) Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab 5:1

    Article  PubMed  PubMed Central  Google Scholar 

  105. Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, Yamada SD, Peter ME, Gwin K, Lengyel E (2011) Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 17:1498–1503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Pascual G, Avgustinova A, Mejetta S, Martin M, Castellanos A, Attolini CS, Berenguer A, Prats N, Toll A, Hueto JA, Bescos C, Di Croce L, Benitah SA (2017) Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 541:41–45

    Article  CAS  PubMed  Google Scholar 

  107. Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, Madeo F (2012) FAT SIGNALS – lipases and lipolysis in lipid metabolism and signaling. Cell Metab 15:279–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. O’Sullivan D, van der Windt GJ, Huang SC, Curtis JD, Chang CH, Buck MD, Qiu J, Smith AM, Lam WY, DiPlato LM, Hsu FF, Birnbaum MJ, Pearce EJ, Pearce EL (2014) Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development. Immunity 41:75–88

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Varga T, Czimmerer Z, Nagy L (1812) PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim Biophys Acta 2011:1007–1022

    Google Scholar 

  110. Chawla A (2010) Control of macrophage activation and function by PPARs. Circ Res 106:1559–1569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Greene ER, Huang S, Serhan CN, Panigrahy D (2011) Regulation of inflammation in cancer by eicosanoids. Prostaglandins Other Lipid Mediat 96:27–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Yan D, Yang Q, Shi M, Zhong L, Wu C, Meng T, Yin H, Zhou J (2013) Polyunsaturated fatty acids promote the expansion of myeloid-derived suppressor cells by activating the JAK/STAT3 pathway. Eur J Immunol 43:2943–2955

    Article  CAS  PubMed  Google Scholar 

  113. Clements VK, Long T, Long R, Figley C, Smith DMC, Ostrand-Rosenberg S (2018) Frontline science: high fat diet and leptin promote tumor progression by inducing myeloid-derived suppressor cells. J Leukoc Biol 103:395–407

    Article  CAS  PubMed  Google Scholar 

  114. Wang D, Dubois RN (2010) Eicosanoids and cancer. Nat Rev Cancer 10:181–193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Kim IW, Myung SJ, Do MY, Ryu YM, Kim MJ, Do EJ, Park S, Yoon SM, Ye BD, Byeon JS, Yang SK, Kim JH (2010) Western-style diets induce macrophage infiltration and contribute to colitis-associated carcinogenesis. J Gastroenterol Hepatol 25:1785–1794

    Article  CAS  PubMed  Google Scholar 

  116. Wallace JM (2002) Nutritional and botanical modulation of the inflammatory cascade – eicosanoids, cyclooxygenases, and lipoxygenases – as an adjunct in cancer therapy. Integr Cancer Ther 1:7–37; discussion

    CAS  PubMed  Google Scholar 

  117. Jia Q, Lupton JR, Smith R, Weeks BR, Callaway E, Davidson LA, Kim W, Fan YY, Yang P, Newman RA, Kang JX, McMurray DN, Chapkin RS (2008) Reduced colitis-associated colon cancer in Fat-1 (n-3 fatty acid desaturase) transgenic mice. Cancer Res 68:3985–3991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Morris DL, Singer K, Lumeng CN (2011) Adipose tissue macrophages: phenotypic plasticity and diversity in lean and obese states. Curr Opin Clin Nutr Metab Care 14:341–346

    Article  PubMed  PubMed Central  Google Scholar 

  120. Hayashi N, Tashiro T, Yamamori H, Takagi K, Morishima Y, Otsubo Y, Sugiura T, Furukawa K, Nitta H, Nakajima N, Suzuki N, Ito I (1999) Effect of intravenous omega-6 and omega-3 fat emulsions on nitrogen retention and protein kinetics in burned rats. Nutrition 15:135–139

    Article  CAS  PubMed  Google Scholar 

  121. Khair-el-Din TA, Sicher SC, Vazquez MA, Wright WJ, Lu CY (1995) Docosahexaenoic acid, a major constituent of fetal serum and fish oil diets, inhibits IFN gamma-induced Ia-expression by murine macrophages in vitro. J Immunol 154:1296–1306

    CAS  PubMed  Google Scholar 

  122. Hughes DA, Southon S (1996) Pinder AC: (n-3) Polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes in vitro. J Nutr 126:603–610

    Article  CAS  PubMed  Google Scholar 

  123. Hughes DA, Pinder AC (1997) N-3 polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibit antigen-presentation in vitro. Clin Exp Immunol 110:516–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Hubbard NE, Somers SD, Erickson KL (1991) Effect of dietary fish oil on development and selected functions of murine inflammatory macrophages. J Leukoc Biol 49:592–598

    Article  CAS  PubMed  Google Scholar 

  125. Sadeghi S, Wallace FA, Calder PC (1999) Dietary lipids modify the cytokine response to bacterial lipopolysaccharide in mice. Immunology 96:404–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Peterson LD, Thies F, Sanderson P, Newsholme EA, Calder PC (1998) Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes. Life Sci 62:2209–2217

    Article  CAS  PubMed  Google Scholar 

  127. Ghosh S, Novak EM, Innis SM (2007) Cardiac proinflammatory pathways are altered with different dietary n-6 linoleic to n-3 alpha-linolenic acid ratios in normal, fat-fed pigs. Am J Physiol Heart Circ Physiol 293:H2919–H2927

    Article  CAS  PubMed  Google Scholar 

  128. Patterson E, Wall R, Fitzgerald GF, Ross RP, Stanton C (2012) Health implications of high dietary omega-6 polyunsaturated fatty acids. J Nutr Metab 2012:539426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Naveena B, Janakiram AM, Lang ML, Rao CV (2015) Immune modulation by agents used in the prevention and treatment of colon and pancreatic cancers. In: Rezaei N (eds) Cancer immunology. Springer, Berlin, Heidelberg, pp 249–275

    Google Scholar 

  130. Fitzgerald-Bocarsly P, Dai J, Singh S (2008) Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history. Cytokine Growth Factor Rev 19:3–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Szebeni GJ, Vizler C, Kitajka K, Puskas LG (2017) Inflammation and cancer: extra- and intracellular determinants of tumor-associated macrophages as tumor promoters. Mediat Inflamm 2017:9294018

    Article  CAS  Google Scholar 

  132. Talmadge JE, Gabrilovich DI (2013) History of myeloid-derived suppressor cells. Nat Rev Cancer 13:739–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58:49–59

    Article  CAS  PubMed  Google Scholar 

  134. Ostrand-Rosenberg S, Fenselau C (2018) Myeloid-derived suppressor cells: immune-suppressive cells that impair antitumor immunity and are sculpted by their environment. J Immunol 200:422–431

    Article  CAS  PubMed  Google Scholar 

  135. Corzo CA, Condamine T, Lu L, Cotter MJ, Youn JI, Cheng P, Cho HI, Celis E, Quiceno DG, Padhya T, McCaffrey TV, McCaffrey JC, Gabrilovich DI (2010) HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med 207:2439–2453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, Mandruzzato S, Murray PJ, Ochoa A, Ostrand-Rosenberg S, Rodriguez PC, Sica A, Umansky V, Vonderheide RH, Gabrilovich DI (2016) Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 7:12150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Anani W, Shurin MR (2017) Targeting myeloid-derived suppressor cells in cancer. Adv Exp Med Biol 1036:105–128

    Article  CAS  PubMed  Google Scholar 

  138. Ostrand-Rosenberg S, Sinha P, Beury DW, Clements VK (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22:275–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Appleby LJ, Nausch N, Heard F, Erskine L, Bourke CD, Midzi N, Mduluza T, Allen JE, Mutapi F (2015) Down regulation of the TCR complex CD3zeta-chain on CD3+ T cells: a potential mechanism for helminth-mediated immune modulation. Front Immunol 6:51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Salminen A, Kauppinen A, Kaarniranta K (2019) AMPK activation inhibits the functions of myeloid-derived suppressor cells (MDSC): impact on cancer and aging. J Mol Med (Berl) 97:1049–1064

    Article  CAS  Google Scholar 

  141. Waight JD, Netherby C, Hensen ML, Miller A, Hu Q, Liu S, Bogner PN, Farren MR, Lee KP, Liu K, Abrams SI (2013) Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. J Clin Invest 123:4464–4478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Lin A, Wang G, Zhao H, Zhang Y, Han Q, Zhang C, Tian Z, Zhang J (2016) TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells. Onco Targets Ther 5:e1074376

    Google Scholar 

  143. Obermajer N, Wong JL, Edwards RP, Odunsi K, Moysich K, Kalinski P (2012) PGE(2)-driven induction and maintenance of cancer-associated myeloid-derived suppressor cells. Immunol Investig 41:635–657

    Article  CAS  Google Scholar 

  144. Abe F, Donkor M, Scholar E, Younos I, Dafferner A, Westphal S, Hoke T, Talmadge J (2009) Chemoprevention by cyclooxygenase-2 inhibition in FVB transgenic mice for Her2/neu induced mammary cancer is associated with reduced myeloid derived suppressor cells. Cancer Prev Res (Phila Pa) 7: 140–151

    Google Scholar 

  145. Levine AG, Hemmers S, Baptista AP, Schizas M, Faire MB, Moltedo B, Konopacki C, Schmidt-Supprian M, Germain RN, Treuting PM, Rudensky AY (2017) Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity. J Exp Med 214:609–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Seddiki N, Santner-Nanan B, Martinson J, Zaunders J, Sasson S, Landay A, Solomon M, Selby W, Alexander SI, Nanan R, Kelleher A (2006) Fazekas de St Groth B: expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203:1693–1700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, Fazekas de St Groth B, Clayberger C, Soper DM, Ziegler SF, Bluestone JA (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Tarhini AA, Butterfield LH, Shuai Y, Gooding WE, Kalinski P, Kirkwood JM (2012) Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-CTLA4 antibody and interferon-alpha or TLR-9 agonist and GM-CSF with peptide vaccination. J Immunother 35:702–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Chao JL, Savage PA (2018) Unlocking the complexities of tumor-associated regulatory T-cells. J Immunol 200:415–421

    Article  CAS  PubMed  Google Scholar 

  150. Spellman A, Tang SC (2016) Immunotherapy for breast cancer: past, present, and future. Cancer Metastasis Rev 35:525–546

    Article  CAS  PubMed  Google Scholar 

  151. Seledtsov VI, Goncharov AG, Seledtsova GV (2015) Clinically feasible approaches to potentiating cancer cell-based immunotherapies. Hum Vaccin Immunother 11:851–869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X, Treuting P, Siewe L, Roers A, Henderson WR Jr, Muller W, Rudensky AY (2008) Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28:546–558

    Article  CAS  PubMed  Google Scholar 

  153. Basil MC, Levy BD (2016) Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol 16:51–67

    Article  CAS  PubMed  Google Scholar 

  154. Serhan CN, Chiang N, Dalli J (2015) The resolution code of acute inflammation: novel pro-resolving lipid mediators in resolution. Semin Immunol 27:200–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Costabile M, Hii CS, Robinson BS, Rathjen DA, Pitt M, Easton C, Miller RC, Poulos A, Murray AW, Ferrante A (2001) A novel long chain polyunsaturated fatty acid, beta-Oxa 21:3n-3, inhibits T lymphocyte proliferation, cytokine production, delayed-type hypersensitivity, and carrageenan-induced paw reaction and selectively targets intracellular signals. J Immunol 167:3980–3987

    Article  CAS  PubMed  Google Scholar 

  156. Arrington JL, Chapkin RS, Switzer KC, Morris JS, McMurray DN (2001) Dietary n-3 polyunsaturated fatty acids modulate purified murine T-cell subset activation. Clin Exp Immunol 125:499–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Ariel A, Chiang N, Arita M, Petasis NA, Serhan CN (2003) Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-alpha secretion from human T cells. J Immunol 170:6266–6272

    Article  CAS  PubMed  Google Scholar 

  158. Chiurchiu V, Leuti A, Dalli J, Jacobsson A, Battistini L, Maccarrone M, Serhan CN (2016) Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses. Sci Transl Med 8:353ra111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  159. Tager AM, Bromley SK, Medoff BD, Islam SA, Bercury SD, Friedrich EB, Carafone AD, Gerszten RE, Luster AD (2003) Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol 4:982–990

    Article  CAS  PubMed  Google Scholar 

  160. Ahima RS (2011) Digging deeper into obesity. J Clin Invest 121:2076–2079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Vlassov AV, Magdaleno S, Setterquist R, Conrad R (1820) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 2012:940–948

    Google Scholar 

  162. Galic S, Oakhill JS, Steinberg GR (2010) Adipose tissue as an endocrine organ. Mol Cell Endocrinol 316:129–139

    Article  CAS  PubMed  Google Scholar 

  163. de Luca C, Olefsky JM (2008) Inflammation and insulin resistance. FEBS Lett 582:97–105

    Article  PubMed  CAS  Google Scholar 

  164. Correa LH, Correa R, Farinasso CM, de Sant’Ana Dourado LP, Magalhaes KG (2017) Adipocytes and macrophages interplay in the orchestration of tumor microenvironment: new implications in cancer progression. Front Immunol 8:1129

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. Roberts DL, Dive C, Renehan AG (2010) Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med 61:301–316

    Article  CAS  PubMed  Google Scholar 

  166. Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347–355

    Article  CAS  PubMed  Google Scholar 

  167. Vona-Davis L, Rose DP (2013) The obesity-inflammation-eicosanoid axis in breast cancer. J Mammary Gland Biol Neoplasia 18:291–307

    Article  PubMed  Google Scholar 

  168. Ben-Neriah Y, Karin M (2011) Inflammation meets cancer, with NF-kappaB as the matchmaker. Nat Immunol 12:715–723

    Article  CAS  PubMed  Google Scholar 

  169. Honma S, Shimodaira K, Shimizu Y, Tsuchiya N, Saito H, Yanaihara T, Okai T (2002) The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells. Endocr J 49:371–377

    Article  CAS  PubMed  Google Scholar 

  170. Norling LV, Serhan CN (2010) Profiling in resolving inflammatory exudates identifies novel anti-inflammatory and pro-resolving mediators and signals for termination. J Intern Med 268:15–24

    CAS  PubMed  Google Scholar 

  171. Gilroy DW, Lawrence T, Perretti M, Rossi AG (2004) Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov 3:401–416

    Article  CAS  PubMed  Google Scholar 

  172. Rueter K, Haynes A, Prescott SL (2015) Developing primary intervention strategies to prevent allergic disease. Curr Allergy Asthma Rep 15:40

    Article  PubMed  CAS  Google Scholar 

  173. Khadge S, Sharp JG, Thiele GM, McGuire TR, Klassen LW, Duryee MJ, Britton HC, Dafferner AJ, Beck J, Black PN, DiRusso CC, Talmadge J (2018) Dietary omega-3 and omega-6 polyunsaturated fatty acids modulate hepatic pathology. J Nutr Biochem 52:92–102

    Article  CAS  PubMed  Google Scholar 

  174. Jackson JD, Yan Y, Brunda MJ, Kelsey LS, Talmadge JE (1995) Interleukin-12 enhances peripheral hematopoiesis in vivo. Blood 85:2371–2376

    Article  CAS  PubMed  Google Scholar 

  175. Rose DP, Connolly JM, Rayburn J, Coleman M (1995) Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice. J Natl Cancer Inst 87:587–592

    Article  CAS  PubMed  Google Scholar 

  176. Khadge S, Thiele GM, Sharp JG, McGuire TR, Klassen LW, Black PN, DiRusso CC, Cook L, Talmadge JE (2018) Long-chain omega-3 polyunsaturated fatty acids decrease mammary tumor growth, multiorgan metastasis and enhance survival. Clin Exp Metastasis 35:797–818

    Article  CAS  PubMed  Google Scholar 

  177. Rose DP, Connolly JM, Coleman M (1996) Effect of omega-3 fatty acids on the progression of metastases after the surgical excision of human breast cancer cell solid tumors growing in nude mice. Clin Cancer Res 2:1751–1756

    CAS  PubMed  Google Scholar 

  178. Mandal CC, Ghosh-Choudhury T, Yoneda T, Choudhury GG, Ghosh-Choudhury N (2010) Fish oil prevents breast cancer cell metastasis to bone. Biochem Biophys Res Commun 402:602–607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Gonzalez MJ, Schemmel RA, Gray JI, Dugan L Jr, Sheffield LG, Welsch CW (1991) Effect of dietary fat on growth of MCF-7 and MDA-MB231 human breast carcinomas in athymic nude mice: relationship between carcinoma growth and lipid peroxidation product levels. Carcinogenesis 12:1231–1235

    Article  CAS  PubMed  Google Scholar 

  180. Talmadge J (2007) Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clin Cancer Res 13:5243–5248

    Article  CAS  PubMed  Google Scholar 

  181. Hardman WE (2007) Dietary canola oil suppressed growth of implanted MDA-MB 231 human breast tumors in nude mice. Nutr Cancer 57:177–183

    Article  CAS  PubMed  Google Scholar 

  182. Sleeman JP (2018) Dietary regulation of metastasis. Clin Exp Metastasis 35:713–714

    Article  CAS  PubMed  Google Scholar 

  183. Manna S, Janarthan M, Ghosh B, Rana B, Rana A, Chatterjee M (2010) Fish oil regulates cell proliferation, protect DNA damages and decrease HER-2/neu and c-Myc protein expression in rat mammary carcinogenesis. Clin Nutr 29:531–537

    Article  CAS  PubMed  Google Scholar 

  184. Noguchi M, Minami M, Yagasaki R, Kinoshita K, Earashi M, Kitagawa H, Taniya T, Miyazaki I (1997) Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA. Br J Cancer 75:348–353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Manna S, Chakraborty T, Ghosh B, Chatterjee M, Panda A, Srivastava S, Rana A, Chatterjee M (2008) Dietary fish oil associated with increased apoptosis and modulated expression of Bax and Bcl-2 during 7,12-dimethylbenz(alpha)anthracene-induced mammary carcinogenesis in rats. Prostaglandins Leukot Essent Fatty Acids 79:5–14

    Article  CAS  PubMed  Google Scholar 

  186. Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56:365–379

    Article  CAS  PubMed  Google Scholar 

  187. Wei N, Wang B, Zhang QY, Mi MT, Zhu JD, Yu XP, Yuan JL, Chen K, Wang J, Chang H (2008) Effects of different dietary fatty acids on the fatty acid compositions and the expression of lipid metabolic-related genes in mammary tumor tissues of rats. Nutr Cancer 60:810–825

    Article  CAS  PubMed  Google Scholar 

  188. Jiang W, Zhu Z, McGinley JN, El Bayoumy K, Manni A, Thompson HJ (2012) Identification of a molecular signature underlying inhibition of mammary carcinoma growth by dietary N-3 fatty acids. Cancer Res 72:3795–3806

    Article  CAS  PubMed  Google Scholar 

  189. Xue M, Wang Q, Zhao J, Dong L, Ge Y, Hou L, Liu Y, Zheng Z (2014) Docosahexaenoic acid inhibited the Wnt/beta-catenin pathway and suppressed breast cancer cells in vitro and in vivo. J Nutr Biochem 25:104–110

    Article  CAS  PubMed  Google Scholar 

  190. Akinsete JA, Ion G, Witte TR, Hardman WE (2012) Consumption of high omega-3 fatty acid diet suppressed prostate tumorigenesis in C3(1) Tag mice. Carcinogenesis 33:140–148

    Article  CAS  PubMed  Google Scholar 

  191. Arber N, DuBois RN (1999) Nonsteroidal anti-inflammatory drugs and prevention of colorectal cancer. Curr Gastroenterol Rep 1:441–448

    Article  CAS  PubMed  Google Scholar 

  192. Hudis CA, Subbaramaiah K, Morris PG, Dannenberg AJ (2012) Breast cancer risk reduction: no pain, no gain? J Clin Oncol 30:3436–3438

    Article  PubMed  Google Scholar 

  193. Restivo A, Cocco IM, Casula G, Scintu F, Cabras F, Scartozzi M, Zorcolo L (2015) Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer. Br J Cancer 113:1133–1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Fontaine E, McShane J, Page R, Shackcloth M, Mediratta N, Carr M, Soorae A, Poullis M (2010) Aspirin and non-small cell lung cancer resections: effect on long-term survival. Eur J Cardiothorac Surg 38:21–26

    Article  PubMed  Google Scholar 

  195. Umar A, Steele VE, Menter DG, Hawk ET (2016) Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention. Semin Oncol 43:65–77

    Article  CAS  PubMed  Google Scholar 

  196. Salinas CA, Kwon EM, FitzGerald LM, Feng Z, Nelson PS, Ostrander EA, Peters U, Stanford JL (2010) Use of aspirin and other nonsteroidal antiinflammatory medications in relation to prostate cancer risk. Am J Epidemiol 172:578–590

    Article  PubMed  PubMed Central  Google Scholar 

  197. Bardia A, Ebbert JO, Vierkant RA, Limburg PJ, Anderson K, Wang AH, Olson JE, Vachon CM, Cerhan JR (2007) Association of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs with cancer incidence and mortality. J Natl Cancer Inst 99:881–889

    Article  CAS  PubMed  Google Scholar 

  198. Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, Meade TW (2010) Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376:1741–1750

    Article  CAS  PubMed  Google Scholar 

  199. Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 231:232–235

    Article  CAS  PubMed  Google Scholar 

  200. Kalgutkar AS, Crews BC, Rowlinson SW, Garner C, Seibert K, Marnett LJ (1998) Aspirin-like molecules that covalently inactivate cyclooxygenase-2. Science 280:1268–1270

    Article  CAS  PubMed  Google Scholar 

  201. Claria J, Serhan CN (1995) Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A 92:9475–9479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Claria J, Lee MH, Serhan CN (1996) Aspirin-triggered lipoxins (15-epi-LX) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Mol Med 2:583–596

    Article  CAS  PubMed  Google Scholar 

  203. Dalli J, Winkler JW, Colas RA, Arnardottir H, Cheng CY, Chiang N, Petasis NA, Serhan CN (2013) Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chem Biol 20:188–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Serhan CN (2014) Pro-resolving lipid mediators are leads for resolution physiology. Nature 510:92–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Serhan CN, Levy BD (2018) Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J Clin Invest 128:2657–2669

    Article  PubMed  PubMed Central  Google Scholar 

  206. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL (2002) Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196:1025–1037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Morris T, Stables M, Colville-Nash P, Newson J, Bellingan G, de Souza PM, Gilroy DW (2010) Dichotomy in duration and severity of acute inflammatory responses in humans arising from differentially expressed proresolution pathways. Proc Natl Acad Sci U S A 107:8842–8847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Simoes RL, De-Brito NM, Cunha-Costa H, Morandi V, Fierro IM, Roitt IM, Barja-Fidalgo C (2017) Lipoxin A4 selectively programs the profile of M2 tumor-associated macrophages which favour control of tumor progression. Int J Cancer 140:346–357

    Article  CAS  PubMed  Google Scholar 

  209. Hu S, Mao-Ying QL, Wang J, Wang ZF, Mi WL, Wang XW, Jiang JW, Huang YL, Wu GC, Wang YQ (2012) Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines. J Neuroinflammation 9:278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Sulciner ML, Serhan CN, Gilligan MM, Mudge DK, Chang J, Gartung A, Lehner KA, Bielenberg DR, Schmidt B, Dalli J, Greene ER, Gus-Brautbar Y, Piwowarski J, Mammoto T, Zurakowski D, Perretti M, Sukhatme VP, Kaipainen A, Kieran MW, Huang S, Panigrahy D (2018) Resolvins suppress tumor growth and enhance cancer therapy. J Exp Med 215:115–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Gilligan MM, Gartung A, Sulciner ML, Norris PC, Sukhatme VP, Bielenberg DR, Huang S, Kieran MW, Serhan CN, Panigrahy D (2019) Aspirin-triggered proresolving mediators stimulate resolution in cancer. Proc Natl Acad Sci U S A 116:6292–6297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Liotta LA, Kohn EC (2001) The microenvironment of the tumour-host interface. Nature 411:375–379

    Article  CAS  PubMed  Google Scholar 

  213. Li H, Fan X, Houghton J (2007) Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem 101:805–815

    Article  CAS  PubMed  Google Scholar 

  214. Jass JR (1986) Lymphocytic infiltration and survival in rectal cancer. J Clin Pathol 39:585–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58:3491–3494

    CAS  PubMed  Google Scholar 

  216. Chiba T, Ohtani H, Mizoi T, Naito Y, Sato E, Nagura H, Ohuchi A, Ohuchi K, Shiiba K, Kurokawa Y, Satomi S (2004) Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis. Br J Cancer 91:1711–1717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964

    Article  CAS  PubMed  Google Scholar 

  218. Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, Platell C, Iacopetta B (2009) Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 27:186–192

    Article  PubMed  Google Scholar 

  219. Sinicrope FA, Rego RL, Ansell SM, Knutson KL, Foster NR, Sargent DJ (2009) Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology 137:1270–1279

    Article  CAS  PubMed  Google Scholar 

  220. Correale P, Rotundo MS, Del Vecchio MT, Remondo C, Migali C, Ginanneschi C, Tsang KY, Licchetta A, Mannucci S, Loiacono L, Tassone P, Francini G, Tagliaferri P (2010) Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy. J Immunother 33:435–441

    Article  PubMed  PubMed Central  Google Scholar 

  221. Deschoolmeester V, Baay M, Van Marck E, Weyler J, Vermeulen P, Lardon F, Vermorken JB (2010) Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients. BMC Immunol 11:19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  222. Chew A, Salama P, Robbshaw A, Klopcic B, Zeps N, Platell C, Lawrance IC (2011) SPARC, FOXP3, CD8 and CD45 correlation with disease recurrence and long-term disease-free survival in colorectal cancer. PLoS One 6:e22047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K (2005) Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 102:18538–18543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Tomsova M, Melichar B, Sedlakova I, Steiner I (2008) Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian carcinoma. Gynecol Oncol 108:415–420

    Article  CAS  PubMed  Google Scholar 

  225. Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, Ellis IO, Green AR (2011) Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 29:1949–1955

    Article  PubMed  Google Scholar 

  226. Liu S, Lachapelle J, Leung S, Gao D, Foulkes WD, Nielsen TO (2012) CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Res 14:R48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Mei Z, Liu Y, Liu C, Cui A, Liang Z, Wang G, Peng H, Cui L, Li C (2014) Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis. Br J Cancer 110:1595–1605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Murff HJ, Shrubsole MJ, Cai Q, Smalley WE, Dai Q, Milne GL, Ness RM, Zheng W (2012) Dietary intake of PUFAs and colorectal polyp risk. Am J Clin Nutr 95:703–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Habermann N, Ulrich CM, Lundgreen A, Makar KW, Poole EM, Caan B, Kulmacz R, Whitton J, Galbraith R, Potter JD, Slattery ML (2013) PTGS1, PTGS2, ALOX5, ALOX12, ALOX15, and FLAP SNPs: interaction with fatty acids in colon cancer and rectal cancer. Genes Nutr 8:115–126

    Article  CAS  PubMed  Google Scholar 

  230. Van Blarigan EL, Fuchs CS, Niedzwiecki D, Ye X, Zhang S, Song M, Saltz LB, Mayer RJ, Mowat RB, Whittom R, Hantel A, Benson A, Atienza D, Messino M, Kindler H, Venook A, Ogino S, Giovannucci EL, Meyerhardt JA (2018) Marine omega-3 polyunsaturated fatty acid and fish intake after colon cancer diagnosis and survival: CALGB 89803 (Alliance). Cancer Epidemiol Biomark Prev 27:438–445

    Article  CAS  Google Scholar 

  231. Mazurak VC (2016) n-3 polyunsaturated fatty acid supplementation during cancer chemotherapy. J Nutr Intermed Metab 5:107–116

    Article  Google Scholar 

  232. Song M, Zhang X, Meyerhardt JA, Giovannucci EL, Ogino S, Fuchs CS, Chan AT (2017) Marine omega-3 polyunsaturated fatty acid intake and survival after colorectal cancer diagnosis. Gut 66:1790–1796

    Article  CAS  PubMed  Google Scholar 

  233. Cockbain AJ, Volpato M, Race AD, Munarini A, Fazio C, Belluzzi A, Loadman PM, Toogood GJ, Hull MA (2014) Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut 63:1760–1768

    Article  CAS  PubMed  Google Scholar 

  234. Schloss I, Kidd MS, Tichelaar HY, Young GO, O’Keefe SJ (1997) Dietary factors associated with a low risk of colon cancer in coloured west coast fishermen. S Afr Med J 87:152–158

    CAS  PubMed  Google Scholar 

  235. Rose DP, Connolly JM (1999) Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 83:217–244

    Article  CAS  PubMed  Google Scholar 

  236. Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, Zaharris E, Macfadyen JG, Danielson E, Lin J, Zhang SM, Buring JE (2012) The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials 33:159–171

    Article  CAS  PubMed  Google Scholar 

  237. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D’Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE, Group VR (2019) Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med 380:23–32

    Article  CAS  PubMed  Google Scholar 

  238. Song M, Nishihara R, Wu K, Qian ZR, Kim SA, Sukawa Y, Mima K, Inamura K, Masuda A, Yang J, Fuchs CS, Giovannucci EL, Ogino S, Chan AT (2015) Marine omega-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability. J Natl Cancer Inst 107

    Google Scholar 

  239. Boland CR, Goel A (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138:2073–87.e3

    Article  CAS  PubMed  Google Scholar 

  240. Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, Blosser RL, Fan H, Wang H, Luber BS, Zhang M, Papadopoulos N, Kinzler KW, Vogelstein B, Sears CL, Anders RA, Pardoll DM, Housseau F (2015) The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 5:43–51

    Article  CAS  PubMed  Google Scholar 

  241. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357:409–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  242. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Song M, Ou FS, Zemla TJ, Hull MA, Shi Q, Limburg PJ, Alberts SR, Sinicrope FA, Giovannucci EL, Van Blarigan EL, Meyerhardt JA, Chan AT (2019) Marine omega-3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance). Int J Cancer 145:380–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Angell H, Galon J (2013) From the immune contexture to the Immunoscore: the role of prognostic and predictive immune markers in cancer. Curr Opin Immunol 25:261–267

    Article  CAS  PubMed  Google Scholar 

  245. Fridman WH, Pages F, Sautes-Fridman C, Galon J (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306

    Article  CAS  PubMed  Google Scholar 

  246. Galon J, Angell HK, Bedognetti D, Marincola FM (2013) The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity 39:11–26

    Article  CAS  PubMed  Google Scholar 

  247. Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353:2654–2666

    Article  CAS  PubMed  Google Scholar 

  248. Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, Nagtegaal ID, Palmqvist R, Masucci GV, Botti G, Tatangelo F, Delrio P, Maio M, Laghi L, Grizzi F, Asslaber M, D’Arrigo C, Vidal-Vanaclocha F, Zavadova E, Chouchane L, Ohashi PS, Hafezi-Bakhtiari S, Wouters BG, Roehrl M, Nguyen L, Kawakami Y, Hazama S, Okuno K, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Wang Y, Kopetz S, Sinicrope FA, Scripcariu V, Ascierto PA, Marincola FM, Fox BA, Pages F (2014) Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 232:199–209

    Article  CAS  PubMed  Google Scholar 

  249. Galon J, Pages F, Marincola FM, Angell HK, Thurin M, Lugli A, Zlobec I, Berger A, Bifulco C, Botti G, Tatangelo F, Britten CM, Kreiter S, Chouchane L, Delrio P, Arndt H, Asslaber M, Maio M, Masucci GV, Mihm M, Vidal-Vanaclocha F, Allison JP, Gnjatic S, Hakansson L, Huber C, Singh-Jasuja H, Ottensmeier C, Zwierzina H, Laghi L, Grizzi F, Ohashi PS, Shaw PA, Clarke BA, Wouters BG, Kawakami Y, Hazama S, Okuno K, Wang E, O’Donnell-Tormey J, Lagorce C, Pawelec G, Nishimura MI, Hawkins R, Lapointe R, Lundqvist A, Khleif SN, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Palmqvist R, Nagtegaal ID, Wang Y, D’Arrigo C, Kopetz S, Sinicrope FA, Trinchieri G, Gajewski TF, Ascierto PA, Fox BA (2012) Cancer classification using the Immunoscore: a worldwide task force. J Transl Med 10:205

    Article  PubMed  PubMed Central  Google Scholar 

  250. Galon J, Pages F, Marincola FM, Thurin M, Trinchieri G, Fox BA, Gajewski TF, Ascierto PA (2012) The immune score as a new possible approach for the classification of cancer. J Transl Med 10:1

    Article  PubMed  PubMed Central  Google Scholar 

  251. Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pages F, Galon J (2011) Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 29:610–618

    Article  PubMed  Google Scholar 

  252. Pages F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, Lagorce C, Wind P, Marliot F, Bruneval P, Zatloukal K, Trajanoski Z, Berger A, Fridman WH, Galon J (2009) In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 27:5944–5951

    Article  CAS  PubMed  Google Scholar 

  253. Zanoaga O, Jurj A, Raduly L, Cojocneanu-Petric R, Fuentes-Mattei E, Wu O, Braicu C, Gherman CD, Berindan-Neagoe I (2018) Implications of dietary omega-3 and omega-6 polyunsaturated fatty acids in breast cancer. Exp Ther Med 15:1167–1176

    CAS  PubMed  Google Scholar 

  254. Chagas TR, Borges DS, de Oliveira PF, Mocellin MC, Barbosa AM, Camargo CQ, Del Moral JAG, Poli A, Calder PC, Trindade E, Nunes EA (2017) Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial. J Hum Nutr Diet 30:681–692

    Article  CAS  PubMed  Google Scholar 

  255. do Carmo LS, Rogero MM, Paredes-Gamero EJ, Nogueira-Pedro A, Xavier JG, Cortez M, Borges MC, Fujii TM, Borelli P, Fock RA (2013) A high-fat diet increases interleukin-3 and granulocyte colony-stimulating factor production by bone marrow cells and triggers bone marrow hyperplasia and neutrophilia in Wistar rats. Exp Biol Med (Maywood) 238:375–384

    Article  CAS  Google Scholar 

  256. Rosales C (2018) Neutrophil: a cell with many roles in inflammation or several cell types? Front Physiol 9:113

    Article  PubMed  PubMed Central  Google Scholar 

  257. Berg JW (1975) Can nutrition explain the pattern of international epidemiology of hormone-dependent cancers? Cancer Res 35:3345–3350

    CAS  PubMed  Google Scholar 

  258. Tominaga S (1985) Cancer incidence in Japanese in Japan, Hawaii, and western United States. Natl Cancer Inst Monogr 69:83–92

    CAS  PubMed  Google Scholar 

  259. Goodstine SL, Zheng T, Holford TR, Ward BA, Carter D, Owens PH, Mayne ST (2003) Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women. J Nutr 133:1409–1414

    Article  CAS  PubMed  Google Scholar 

  260. Calder PC (1997) N-3 polyunsaturated fatty acids and immune cell function. Adv Enzym Regul 37:197–237

    Article  CAS  Google Scholar 

  261. Simonsen N, van’t Veer P, Strain JJ, Martin-Moreno JM, Huttunen JK, Navajas JF, Martin BC, Thamm M, Kardinaal AF, Kok FJ, Kohlmeier L (1998) Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer. Am J Epidemiol 147:342–352

    Article  CAS  PubMed  Google Scholar 

  262. Thiebaut AC, Chajes V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, Benichou J, Clavel-Chapelon F (2009) Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer 124:924–931

    Article  CAS  PubMed  Google Scholar 

  263. Kim J, Lim SY, Shin A, Sung MK, Ro J, Kang HS, Lee KS, Kim SW, Lee ES (2009) Fatty fish and fish omega-3 fatty acid intakes decrease the breast cancer risk: a case-control study. BMC Cancer 9:216

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  264. Khankari NK, Bradshaw PT, Steck SE, He K, Olshan AF, Shen J, Ahn J, Chen Y, Ahsan H, Terry MB, Teitelbaum SL, Neugut AI, Santella RM, Gammon MD (2015) Dietary intake of fish, polyunsaturated fatty acids, and survival after breast cancer: a population-based follow-up study on Long Island, New York. Cancer 121:2244–2252

    Article  CAS  PubMed  Google Scholar 

  265. Bagga D, Anders KH, Wang HJ, Glaspy JA (2002) Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer. Nutr Cancer 42:180–185

    Article  CAS  PubMed  Google Scholar 

  266. Yang B, Ren XL, Fu YQ, Gao JL, Li D (2014) Ratio of n-3/n-6 PUFAs and risk of breast cancer: a meta-analysis of 274135 adult females from 11 independent prospective studies. BMC Cancer 14:105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  267. Im DS (2016) Functions of omega-3 fatty acids and FFA4 (GPR120) in macrophages. Eur J Pharmacol 785:36–43

    Article  CAS  PubMed  Google Scholar 

  268. Bjursell M, Xu X, Admyre T, Bottcher G, Lundin S, Nilsson R, Stone VM, Morgan NG, Lam YY, Storlien LH, Linden D, Smith DM, Bohlooly YM, Oscarsson J (2014) The beneficial effects of n-3 polyunsaturated fatty acids on diet induced obesity and impaired glucose control do not require Gpr120. PLoS One 9:e114942

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  269. Chung H, Lee YS, Mayoral R, Oh DY, Siu JT, Webster NJ, Sears DD, Olefsky JM, Ellies LG (2015) Omega-3 fatty acids reduce obesity-induced tumor progression independent of GPR120 in a mouse model of postmenopausal breast cancer. Oncogene 34:3504–3513

    Article  CAS  PubMed  Google Scholar 

  270. Calder PC (1851) Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta 2015:469–484

    Google Scholar 

  271. Xia S, Li XP, Cheng L, Han MT, Zhang MM, Shao QX, Xu HX, Qi L (2015) Fish oil-rich diet promotes hematopoiesis and alters hematopoietic niche. Endocrinology 156:2821–2830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Schumann T, Adhikary T, Wortmann A, Finkernagel F, Lieber S, Schnitzer E, Legrand N, Schober Y, Nockher WA, Toth PM, Diederich WE, Nist A, Stiewe T, Wagner U, Reinartz S, Muller-Brusselbach S, Muller R (2015) Deregulation of PPARbeta/delta target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment. Oncotarget 6:13416–13433

    Article  PubMed  PubMed Central  Google Scholar 

  273. Wensing AG, Mensink RP, Hornstra G (1999) Effects of dietary n-3 polyunsaturated fatty acids from plant and marine origin on platelet aggregation in healthy elderly subjects. Br J Nutr 82:183–191

    Article  CAS  PubMed  Google Scholar 

  274. Gross BW, Gillio M, Rinehart CD, Lynch CA, Rogers FB (2017) Omega-3 fatty acid supplementation and warfarin: a lethal combination in traumatic brain injury. J Trauma Nurs 24:15–18

    Article  PubMed  Google Scholar 

  275. Buckley MS, Goff AD, Knapp WE (2004) Fish oil interaction with warfarin. Ann Pharmacother 38:50–52

    Article  PubMed  Google Scholar 

  276. Jalili M, Dehpour AR (2007) Extremely prolonged INR associated with warfarin in combination with both trazodone and omega-3 fatty acids. Arch Med Res 38:901–904

    Article  CAS  PubMed  Google Scholar 

  277. McClaskey EM, Michalets EL (2007) Subdural hematoma after a fall in an elderly patient taking high-dose omega-3 fatty acids with warfarin and aspirin: case report and review of the literature. Pharmacotherapy 27:152–160

    Article  CAS  PubMed  Google Scholar 

  278. Stanger MJ, Thompson LA, Young AJ, Lieberman HR (2012) Anticoagulant activity of select dietary supplements. Nutr Rev 70:107–117

    Article  PubMed  Google Scholar 

  279. Harris WS, Silveira S, Dujovne CA (1990) The combined effects of N-3 fatty acids and aspirin on hemostatic parameters in man. Thromb Res 57:517–526

    Article  CAS  PubMed  Google Scholar 

  280. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm LH, Sorlie P, Yancy CW, Rosamond WD (2010) Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond. Circulation 121:586–613

    Article  PubMed  Google Scholar 

  281. Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, Sugimoto Y, Miyazaki S, Tsujimoto G (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 11:90–94

    Article  CAS  PubMed  Google Scholar 

  282. Edwards IJ, O’Flaherty JT (2008) Omega-3 fatty acids and PPARgamma in cancer. PPAR Res 2008:358052

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE, USA

    Saraswoti Khadge, Geoffrey M. Thiele & James E. Talmadge

  2. Vanderbilt University, Nashville, TN, USA

    Saraswoti Khadge

  3. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA

    John Graham Sharp

  4. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    Geoffrey M. Thiele & James E. Talmadge

  5. Veteran Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA

    Geoffrey M. Thiele

  6. Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, USA

    Timothy R. McGuire

Authors
  1. Saraswoti Khadge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John Graham Sharp
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Geoffrey M. Thiele
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Timothy R. McGuire
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James E. Talmadge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James E. Talmadge .

Editor information

Editors and Affiliations

  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Khadge, S., Sharp, J.G., Thiele, G.M., McGuire, T.R., Talmadge, J.E. (2020). Fatty Acid Mediators in the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1259. Springer, Cham. https://doi.org/10.1007/978-3-030-43093-1_8

Download citation

Publish with us

Policies and ethics

Search

Navigation