Abstract
Interaction between inflammation and tumor microenvironment (TME) is known as one of the main causes of cancer development. TME is an intricate network composed of tumor and immune cells, cytokines, enzymes, and other related factors. Pro-inflammatory cytokines, mostly IL-1 family, IL-6, and TNF-α, are key factors in creating chronic inflammation in the tumor context. Based on reported evidence, these cytokines indicate either pro-tumorigenic or anti-tumorigenic functions dependent on cancer type, TME, and other related factors. As the pro-tumorigenic function, the pro-inflammatory cytokines alongside supportive cells and factors lead to hyperinflammation and tumor promotion by affecting different mechanisms, including angiogenesis, proliferation, immunosuppression, extracellular matrix remodeling, invasiveness, and metastasis. Regarding the importance of tumor immunopathogenesis, attracting attention to inflammation and the abovementioned cytokines is critically required. Hence, this study aimed to discuss the role of the pro-inflammatory cytokine in cancers comprehensively, which would help open a window toward depth recognition of cancer pathogenesis and increase the efforts to improve and develop practical cancer therapeutic approaches.
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References
Allen IC, TeKippe EM, Woodford R-MT, Uronis JM, Holl EK, Rogers AB et al (2010) The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 207(5):1045–1056
Ando M, Uehara I, Kogure K, Asano Y, Nakajima W, Abe Y et al (2010) Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3. J Nippon Med School 77(2):97–105
Apte RN, Voronov E (2017) Immunotherapeutic approaches of IL-1 neutralization in the tumor microenvironment. J Leukoc Biol 102(2):293–306
Arnott CH, Scott KA, Moore RJ, Hewer A, Phillips DH, Parker P et al (2002) Tumour necrosis factor-α mediates tumour promotion via a PKCα-and AP-1-dependent pathway. Oncogene 21(31):4728–4738
Baker KJ, Houston A, Brint E (2019) IL-1 family members in cancer; two sides to every story. Front Immunol 10:1197
Balkwill FR, Mantovani A (2012) Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol 22(1):33–40
Bharti R, Dey G, Mandal M (2016) Cancer development, chemoresistance, epithelial to mesenchymal transition and stem cells: a snapshot of IL-6 mediated involvement. Cancer Lett 375(1):51–61
Bhattacharyya S, Mandal D, Sen GS, Pal S, Banerjee S, Lahiry L et al (2007) Tumor-induced oxidative stress perturbs nuclear factor-kappaB activity-augmenting tumor necrosis factor-alpha-mediated T-cell death: protection by curcumin. Cancer Res 67(1):362–370
Biswas SK (2015) Metabolic reprogramming of immune cells in cancer progression. Immunity 43(3):435–449
Briukhovetska D, Dörr J, Endres S, Libby P, Dinarello CA, Kobold S (2021) Interleukins in cancer: from biology to therapy. Nat Rev Cancer 21(8):481–499
Browning L, Patel MR, Horvath EB, Tawara K, Jorcyk CL (2018) IL-6 and ovarian cancer: inflammatory cytokines in promotion of metastasis. Cancer Manag Res 10:6685
Celik A, Bakar-Ates F (2021) The confounding effect of interleukin-6 on apoptosis of MCF-7 cells through down-regulation of MMP-2/−9 mRNA expression. Turk J Biochem 46(5):549–555
Chen Y, Zhang F, Tsai Y, Yang X, Yang L, Duan S et al (2015) IL-6 signaling promotes DNA repair and prevents apoptosis in CD133+ stem-like cells of lung cancer after radiation. Radiat Oncol 10(1):1–10
Chen Y, Wen H, Zhou C, Su Q, Lin Y, Xie Y et al (2019) TNF-α derived from M2 tumor-associated macrophages promotes epithelial-mesenchymal transition and cancer stemness through the Wnt/β-catenin pathway in SMMC-7721 hepatocellular carcinoma cells. Exp Cell Res 378(1):41–50
Chonov DC, Ignatova MMK, Ananiev JR, Gulubova MV (2019) IL-6 activities in the tumour microenvironment. Part 1. Open Access Maced J Med Sci 7(14):2391
Coca S, Perez-Piqueras J, Martinez D, Colmenarejo A, Saez MA, Vallejo C et al (1997) The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 79(12):2320–2328
Comen E, Wojnarowicz P, Seshan VE, Shah R, Coker C, Norton L et al (2016) TNF is a key cytokine mediating neutrophil cytotoxic activity in breast cancer patients. NPJ Breast Cancer 2:16009
Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87(6):2095–2147
Dinarello CA (2006) The paradox of pro-inflammatory cytokines in cancer. Cancer Metastasis Rev 25(3):307–313
Du Z, Lovly CM (2018) Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer 17(1):58
Fajardo LF, Kwan HH, Kowalski J, Prionas SD, Allison AC (1992) Dual role of tumor necrosis factor-alpha in angiogenesis. Am J Pathol 140(3):539–544
Greenwel P, Tanaka S, Penkov D, Zhang W, Olive M, Moll J et al (2000) Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins. Mol Cell Biol 20(3):912–918
Grivennikov SI (2013) Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol 35(2):229–244
Hirano S, Kataoka T (2013) Deoxynivalenol induces ectodomain shedding of TNF receptor 1 and thereby inhibits the TNF-α-induced NF-κB signaling pathway. Eur J Pharmacol 701(1–3):144–151
Holen I, Lefley DV, Francis SE, Rennicks S, Bradbury S, Coleman RE et al (2016) IL-1 drives breast cancer growth and bone metastasis in vivo. Oncotarget 7(46):75571
Huerta-Yepez S, Vega M, Garban H, Bonavida B (2006) Involvement of the TNF-alpha autocrine-paracrine loop, via NF-kappaB and YY1, in the regulation of tumor cell resistance to Fas-induced apoptosis. Clin Immunol (Orlando, Fla) 120(3):297–309
Jones SA, Scheller J, Rose-John S (2011) Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest 121(9):3375–3383
Kang JS, Y. Bae S, H. Kim R, Kim YS, J. Kim D, Cho BJ et al (2009) Interleukin-18 increases metastasis and immune escape of stomach cancer via the downregulation of CD70 and maintenance of CD44. Carcinogenesis 30(12):1987–1996
Kaplanski G, Farnarier C, Kaplanski S, Porat R, Shapiro L, Bongrand P et al (1994) Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism. Blood 84:4242–4248
Kawada M, Ishizuka M, Takeuchi T (1999) Enhancement of antiproliferative effects of interleukin-1β and tumor necrosis factor-α on human prostate cancer LNCaP cells by coculture with normal fibroblasts through secreted interleukin-6. Jpn J Cancer Res 90(5):546–554
Kim K, Song H, Kim TS, Yoon D, Kim C, Bang S et al (2007) Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines. Oncogene 26(10):1468–1476
Kim J, Lee J, Oh JH, Chang HJ, Sohn DK, Shin A et al (2019) Circulating interleukin-6 level, dietary antioxidant capacity, and risk of colorectal cancer. Antioxidants 8(12):595
Kumari N, Dwarakanath B, Das A, Bhatt AN (2016) Role of interleukin-6 in cancer progression and therapeutic resistance. Tumor Biol 37(9):11553–11572
Laha D, Grant R, Mishra P, Nilubol N (2021) The role of tumor necrosis factor in manipulating the immunological response of tumor microenvironment. Front Immunol 12:656908
Lan T, Chen L, Wei X (2021) Inflammatory cytokines in cancer: comprehensive understanding and clinical progress in gene therapy. Cells 10(1):100
Laronha H, Caldeira J (2020) Structure and function of human matrix metalloproteinases. Cells 9(5):1076
Letterio JJ, Roberts AB (1998) Regulation of immune responses by TGF-beta. Annu Rev Immunol 16:137–161
Li L, Hong Z (2016) IL-1β/NF-kb signaling promotes colorectal cancer cell growth through miR-181a/PTEN axis. Arch Biochem Biophys 604:20–26
Li Y, Wang L, Pappan L, Galliher-Beckley A, Shi J (2012) IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Mol Cancer 11(1):1–13
Lin Y, He Z, Ye J, Liu Z, She X, Gao X et al (2020) Progress in understanding the IL-6/STAT3 pathway in colorectal cancer. Onco Targets Ther 13:13023
Liu S, Lee JS, Jie C, Park MH, Iwakura Y, Patel Y et al (2018) HER2 overexpression triggers an IL1α proinflammatory circuit to drive tumorigenesis and promote chemotherapy resistance. Cancer Res 78(8):2040–2051
Luo JL, Maeda S, Hsu LC, Yagita H, Karin M (2004) Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell 6(3):297–305
Mantovani A, Barajon I, Garlanda C (2018) IL-1 and IL-1 regulatory pathways in cancer progression and therapy. Immunol Rev 281(1):57–61
Mercogliano MF, Bruni S, Mauro F, Elizalde PV, Schillaci R (2021) Harnessing tumor necrosis factor alpha to achieve effective cancer immunotherapy. Cancers 13(3):564
Mikesh LM, Kumar M, Erdag G, Hogan KT, Molhoek KR, Mayo MW et al (2010) Evaluation of molecular markers of mesenchymal phenotype in melanoma. Melanoma Res 20(6):485–495
Mittal V (2018) Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol 13:395–412
Nakamura K, Kassem S, Cleynen A, Chrétien M-L, Guillerey C, Putz EM et al (2018) Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment. Cancer Cell. 33(4):634–48.e5
Oh K, Lee O-Y, Park Y, Seo MW, Lee D-S (2016) IL-1β induces IL-6 production and increases invasiveness and estrogen-independent growth in a TG2-dependent manner in human breast cancer cells. BMC Cancer 16(1):1–11
Pileczki V, Braicu C, Gherman CD, Berindan-Neagoe I (2012) TNF-α gene knockout in triple negative breast cancer cell line induces apoptosis. Int J Mol Sci 14(1):411–420
Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D et al (2009) Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A 106(35):14978–14983
Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF et al (2013) CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med 19(10):1264–1272
Radharani N, Yadav AS, Nimma R, Kumar T, Bulbule A, Chanukuppa V et al (2022) Tumor-associated macrophage derived IL-6 enriches cancer stem cell population and promotes breast tumor progression via Stat-3 pathway. Cancer Cell Int 22(1):1–19
Rider P, Carmi Y, Voronov E, Apte RN, editors (2013) Interleukin-1α. Seminars in immunology. Elsevier
Sabio G, Davis RJ (2014) TNF and MAP kinase signalling pathways. Semin Immunol 26(3):237–245
Sade-Feldman M, Kanterman J, Ish-Shalom E, Elnekave M, Horwitz E, Baniyash M (2013) Tumor necrosis factor-α blocks differentiation and enhances suppressive activity of immature myeloid cells during chronic inflammation. Immunity 38(3):541–554
Sasi SP, Yan X, Enderling H, Park D, Gilbert HY, Curry C et al (2012) Breaking the ‘harmony’ of TNF-α signaling for cancer treatment. Oncogene 31(37):4117–4127
Sawai H, Funahashi H, Yamamoto M, Okada Y, Hayakawa T, Tanaka M et al (2003) Interleukin-1α enhances integrin α6β1 expression and metastatic capability of human pancreatic cancer. Oncology 65(2):167–173
Schweighofer B, Testori J, Sturtzel C, Sattler S, Mayer H, Wagner O et al (2009) The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation. Thromb Haemost 102(09):544–554
Soria G, Ofri-Shahak M, Haas I, Yaal-Hahoshen N, Leider-Trejo L, Leibovich-Rivkin T et al (2011) Inflammatory mediators in breast cancer: coordinated expression of TNFα & IL-1β with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition. BMC Cancer 11:130
Sun R, Luo J, Li D, Shu Y, Luo C, Wang SS et al (2014) Neutrophils with protumor potential could efficiently suppress tumor growth after cytokine priming and in presence of normal NK cells. Oncotarget 5(24):12621–12634
Tang D, Tao D, Fang Y, Deng C, Xu Q, Zhou J (2017) TNF-alpha promotes invasion and metastasis via NF-kappa B pathway in oral squamous cell carcinoma. Med Sci Monit Basic Res 23:141–149
Taniguchi K, Karin M (2018) NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol 18(5):309–324
Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y et al (2003) IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci 100(5):2645–2650
Voronov E, Carmi Y, Apte RN (2014) The role IL-1 in tumor-mediated angiogenesis. Front Physiol 5:114
Wang H, Wang HS, Zhou BH, Li CL, Zhang F, Wang XF et al (2013) Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer. PLoS One 8(2):e56664
Wang Y, Wang Y, Duan X, Wang Y, Zhang Z (2018) Interleukin-1 receptor-associated kinase 1 correlates with metastasis and invasion in endometrial carcinoma. J Cell Biochem 119(3):2545–2555
Weber A, Wasiliew P, Kracht M (2010) Interleukin-1β (IL-1β) processing pathway. Sci Signal 3(105):cm1–cm1
Weichand B, Popp R, Dziumbla S, Mora J, Strack E, Elwakeel E et al (2017) S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1β. J Exp Med 214(9):2695–2713
Yamane K, Ihn H, Asano Y, Jinnin M, Tamaki K (2003) Antagonistic effects of TNF-alpha on TGF-beta signaling through down-regulation of TGF-beta receptor type II in human dermal fibroblasts. J Immunol (Baltimore, Md: 1950) 171(7):3855–3862
Yan B, Wang H, Rabbani ZN, Zhao Y, Li W, Yuan Y et al (2006) Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation. Cancer Res 66(24):11565–11570
Yang H, Bocchetta M, Kroczynska B, Elmishad AG, Chen Y, Liu Z et al (2006) TNF-α inhibits asbestos-induced cytotoxicity via a NF-κB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proc Natl Acad Sci 103(27):10397–10402
Yi M, Ban Y, Tan Y, Xiong W, Li G, Xiang B (2019) 6-Phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 and 4: a pair of valves for fine-tuning of glucose metabolism in human cancer. Mol Metab 20:1–13
Zhang G, Liu Z, Han Y, Wang X, Yang Z (2016) Overexpression of miR-509 increases apoptosis and inhibits invasion via suppression of tumor necrosis factor-α in triple-negative breast cancer Hs578T cells. Oncol Res 24(4):233–238
Zhao Y, Yang F, Li W, Xu C, Li L, Chen L et al (2017) miR-29a suppresses MCF-7 cell growth by downregulating tumor necrosis factor receptor 1. Tumour Biol 39(2):1010428317692264
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Tahmasebi, S., Alimohammadi, M., Khorasani, S., Rezaei, N. (2023). Pro-tumorigenic and Anti-tumorigenic Roles of Pro-inflammatory Cytokines in Cancer. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_25-1
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DOI: https://doi.org/10.1007/978-3-030-80962-1_25-1
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