Skip to main content
SpringerLink
Log in

Immunosuppressive Tumor Microenvironment Status and Histological Grading of Endometrial Carcinoma

  • Original Article
  • Published:
Cancer Microenvironment

Abstract

The recent successes of new cancer immunotherapy approaches have led to investigate their relevance in the context of the Endometrial Carcinoma (EC). These therapies, that take the tumor-induced immunosuppressive microenvironment into account, target the tumor immune escape, in particular the inhibitory receptors involved in the regulation of the effector T cells’ activity (immune checkpoints). The aim of this study was to identify, in ECs, differences in intergrades immune status that could contribute to the differences in tumor aggressiveness, and could also be used as theranostic tools. The immune status of tumors was assessed by quantitative real-time PCR. We analyzed the expression of specific genes associated to specific leukocytes subpopulations and the expression of reporting genes associated with the tumor escape/resistance. This study highlights significant differences in the EC intergrades immune status especially the tumor-infiltrating cell types and their activation status as well as in the molecular factors produced by the environment. The immune microenvironment of grade 1 ECs hints at a robust tumoricidal milieu while that of higher grades is more evocative of a tolerogenic milieu. This genes-based immunological monitoring of tumors that easily highlights significant intergrade differences relating to the density, composition and functional state of the leukocyte infiltrate, could give solid arguments for choosing the best therapeutic options, especially those targeting immune checkpoints. Moreover it could enable an easy adaptation of individual treatment approaches for each patient.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. https://doi.org/10.1002/ijc.29210

    Article  CAS  PubMed  Google Scholar 

  2. Shim SH, Kim DY, Kim HJ, Lee SW, Park JY, Suh DS, Kim JH, Kim YM, Kim YT, Nam JH (2017) Stratification of risk groups according to survival after recurrence in endometrial cancer patients. Medicine (Baltimore) 96(21):e6920. https://doi.org/10.1097/MD.0000000000006920

    Article  CAS  Google Scholar 

  3. Tran AQ, Gehrig P (2017) Recent advances in endometrial Cancer. F1000Res 6:81. https://doi.org/10.12688/f1000research.10020.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MDM, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L (2013) Mutational landscape and significance across 12 major cancer types. Nature 502(7471):333–339. https://doi.org/10.1038/nature12634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Stelloo E, Bosse T, Nout RA, MacKay HJ, Church DN, Nijman HW, Leary A, Edmondson RJ, Powell ME, Crosbie EJ, Kitchener HC, Mileshkin L, Pollock PM, Smit VT, Creutzberg CL (2015) Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol 28(6):836–844. https://doi.org/10.1038/modpathol.2015.43

    Article  CAS  PubMed  Google Scholar 

  6. Balkwill FR, Capasso M, Hagemann T (2012) The tumor microenvironment at a glance. J Cell Sci 125 (Pt 23:5591–5596. https://doi.org/10.1242/jcs.116392

    Article  CAS  PubMed  Google Scholar 

  7. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264. https://doi.org/10.1038/nrc3239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S (2015) Ribas a, investigators K- (2015) Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med 372(26):2521–2532. https://doi.org/10.1056/NEJMoa1503093

    Article  CAS  PubMed  Google Scholar 

  9. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34. https://doi.org/10.1056/NEJMoa1504030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P, CheckMate I (2015) Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med 373(19):1803–1813. https://doi.org/10.1056/NEJMoa1510665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA (2016) PD-1 blockade with Pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med 374(26):2542–2552. https://doi.org/10.1056/NEJMoa1603702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung Cancer. N Engl J Med 373(17):1627–1639. https://doi.org/10.1056/NEJMoa1507643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Manson G, Norwood J, Marabelle A, Kohrt H, Houot R (2016) Biomarkers associated with checkpoint inhibitors) Annals of oncology : official journal of the European society for. Medical Oncology / ESMO 27(7):1199–1206. https://doi.org/10.1093/annonc/mdw181

    Article  CAS  Google Scholar 

  14. Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH (2016) Coinhibitory pathways in immunotherapy for Cancer. Annu Rev Immunol 34:539–573. https://doi.org/10.1146/annurev-immunol-032414-112049

    Article  CAS  PubMed  Google Scholar 

  15. Mahoney KM, Rennert PD, Freeman GJ (2015) Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 14(8):561–584. https://doi.org/10.1038/nrd4591

    Article  CAS  PubMed  Google Scholar 

  16. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD (2016) The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol 13(5):273–290. https://doi.org/10.1038/nrclinonc.2016.25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, Iyer AK (2017) PD-1 and PD-L1 checkpoint signaling inhibition for Cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol 8:561. https://doi.org/10.3389/fphar.2017.00561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hughes PE, Caenepeel S, Wu LC (2016) Targeted therapy and checkpoint immunotherapy combinations for the treatment of Cancer. Trends Immunol 37(7):462–476. https://doi.org/10.1016/j.it.2016.04.010

    Article  CAS  PubMed  Google Scholar 

  19. Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E (2016) Endometrial cancer. Lancet 387(10023):1094–1108. https://doi.org/10.1016/S0140-6736(15)00130-0

    Article  PubMed  Google Scholar 

  20. Vanderstraeten A, Luyten C, Verbist G, Tuyaerts S, Amant F (2014) Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy. Cancer Immunol Immunother 63(6):545–557. https://doi.org/10.1007/s00262-014-1537-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Herzog TJ, Arguello D, Reddy SK, Gatallica Z (2015) PD-1, PD-L1 expression in 1599 gynecological cancers: implications for immunotherapy. Gynecol Oncol 137 (Supplement 1:204–205. https://doi.org/10.1016/j.ygyno.2015.01.514

    Article  Google Scholar 

  22. Howitt BE, Shukla SA, Sholl LM, Ritterhouse LL, Watkins JC, Rodig S, Stover E, Strickland KC, D'Andrea AD, Wu CJ, Matulonis UA, Konstantinopoulos PA (2015) Association of Polymerase e-mutated and microsatellite-instable endometrial cancers with Neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol 1(9):1319–1323. https://doi.org/10.1001/jamaoncol.2015.2151

    Article  PubMed  Google Scholar 

  23. Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, Puzanov I, Mehnert JM, Aung KL, Lopez J, Carrigan M, Saraf S, Chen M, Soria JC (2017) Safety and antitumor activity of Pembrolizumab in advanced programmed death ligand 1-positive endometrial Cancer: results from the KEYNOTE-028 study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 35(22):2535–2541. https://doi.org/10.1200/JCO.2017.72.5952

    Article  CAS  Google Scholar 

  24. 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 (26):2509–2520. doi:https://doi.org/10.1056/NEJMoa1500596

    Article  CAS  PubMed  Google Scholar 

  25. Kurman RJ, International Agency for Research on Cancer, World Health Organization (2014) WHO classification of tumours of female reproductive organs. World Health Organization classification of tumours, 4th edn. International Agency for Research on Cancer, Lyon

    Google Scholar 

  26. Creasman W (2009) Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet 105(2):109. https://doi.org/10.1016/j.ijgo.2009.02.010

    Article  PubMed  Google Scholar 

  27. Mocellin S, Provenzano M, Rossi CR, Pilati P, Nitti D, Lise M (2003) Use of quantitative real-time PCR to determine immune cell density and cytokine gene profile in the tumor microenvironment. J Immunol Methods 280(1–2):1–11

    Article  CAS  PubMed  Google Scholar 

  28. Danaher P, Warren S, Dennis L, D'Amico L, White A, Disis ML, Geller MA, Odunsi K, Beechem J, Fling SP (2017) Gene expression markers of tumor infiltrating leukocytes. Journal for immunotherapy of cancer 5:18. https://doi.org/10.1186/s40425-017-0215-8

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cernadas M, Lu J, Watts G, Brenner MB (2009) CD1a expression defines an interleukin-12 producing population of human dendritic cells. Clin Exp Immunol 155(3):523–533. https://doi.org/10.1111/j.1365-2249.2008.03853.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jimenez F, Quinones MP, Martinez HG, Estrada CA, Clark K, Garavito E, Ibarra J, Melby PC, Ahuja SS (2010) CCR2 plays a critical role in dendritic cell maturation: possible role of CCL2 and NF-kappa B. J Immunol 184(10):5571–5581. https://doi.org/10.4049/jimmunol.0803494

    Article  CAS  PubMed  Google Scholar 

  31. Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19(11):1423–1437. https://doi.org/10.1038/nm.3394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 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. https://doi.org/10.1111/imr.12614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mizukami Y, Kono K, Kawaguchi Y, Akaike H, Kamimura K, Sugai H, Fujii H (2008) CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer. Int J Cancer 122(10):2286–2293. https://doi.org/10.1002/ijc.23392

    Article  CAS  PubMed  Google Scholar 

  34. 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 (2006) Pages F (2006) type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964

    Article  CAS  PubMed  Google Scholar 

  35. Erdag G, Schaefer JT, Smolkin ME, Deacon DH, Shea SM, Dengel LT, Patterson JW, Slingluff CL Jr (2012) Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res 72(5):1070–1080. https://doi.org/10.1158/0008-5472.CAN-11-3218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Manaster I, Mandelboim O (2010) The unique properties of uterine NK cells. Am J Reprod Immunol 63(6):434–444. https://doi.org/10.1111/j.1600-0897.2009.00794.x

    Article  CAS  PubMed  Google Scholar 

  37. Vanderstraeten A, Tuyaerts S, Amant F (2015) The immune system in the normal endometrium and implications for endometrial cancer development. J Reprod Immunol 109:7–16. https://doi.org/10.1016/j.jri.2014.12.006

    Article  CAS  PubMed  Google Scholar 

  38. Jago CB, Yates J, Camara NO, Lechler RI, Lombardi G (2004) Differential expression of CTLA-4 among T cell subsets. Clin Exp Immunol 136(3):463–471. https://doi.org/10.1111/j.1365-2249.2004.02478.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gao J, Shi LZ, Zhao H, Chen J, Xiong L, He Q, Chen T, Roszik J, Bernatchez C, Woodman SE, Chen PL, Hwu P, Allison JP, Futreal A, Wargo JA, Sharma P (2016) Loss of IFN-gamma pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell 167(2):397–404 e399. https://doi.org/10.1016/j.cell.2016.08.069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Liakou CI, Kamat A, Tang DN, Chen H, Sun J, Troncoso P, Logothetis C, Sharma P (2008) CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci U S A 105(39):14987–14992. https://doi.org/10.1073/pnas.0806075105

    Article  PubMed  PubMed Central  Google Scholar 

  41. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, Saco J, Homet Moreno B, Mezzadra R, Chmielowski B, Ruchalski K, Shintaku IP, Sanchez PJ, Puig-Saus C, Cherry G, Seja E, Kong X, Pang J, Berent-Maoz B, Comin-Anduix B, Graeber TG, Tumeh PC, Schumacher TN, Lo RS, Ribas A (2016) Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med 375(9):819–829. https://doi.org/10.1056/NEJMoa1604958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shi L, Chen S, Yang L, Li Y (2013) The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol 6(1):74. https://doi.org/10.1186/1756-8722-6-74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Taylor NA, Vick SC, Iglesia MD, Brickey WJ, Midkiff BR, McKinnon KP, Reisdorf S, Anders CK, Carey LA, Parker JS, Perou CM, Vincent BG, Serody JS (2017) Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer. J Clin Invest 127(9):3472–3483. https://doi.org/10.1172/JCI90499

    Article  PubMed  PubMed Central  Google Scholar 

  44. Anderson AC, Joller N, Kuchroo VK (2016) Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity 44(5):989–1004. https://doi.org/10.1016/j.immuni.2016.05.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ferris RL, Lu B, Kane LP (2014) Too much of a good thing? Tim-3 and TCR signaling in T cell exhaustion. J Immunol 193(4):1525–1530. https://doi.org/10.4049/jimmunol.1400557

    Article  CAS  PubMed  Google Scholar 

  46. Banerjee H, Kane LP (2018) Immune regulation by Tim-3. F1000Res 7:316. https://doi.org/10.12688/f1000research.13446.1

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zhou X, Sun L, Jing D, Xu G, Zhang J, Lin L, Zhao J, Yao Z, Lin H (2018) Galectin-9 expression predicts favorable clinical outcome in solid tumors: a systematic review and meta-analysis. Front Physiol 9:452. https://doi.org/10.3389/fphys.2018.00452

    Article  PubMed  PubMed Central  Google Scholar 

  48. Dai SY, Nakagawa R, Itoh A, Murakami H, Kashio Y, Abe H, Katoh S, Kontani K, Kihara M, Zhang SL, Hata T, Nakamura T, Yamauchi A, Hirashima M (2005) Galectin-9 induces maturation of human monocyte-derived dendritic cells. J Immunol 175(5):2974–2981

    Article  CAS  PubMed  Google Scholar 

  49. Nagahara K, Arikawa T, Oomizu S, Kontani K, Nobumoto A, Tateno H, Watanabe K, Niki T, Katoh S, Miyake M, Nagahata S, Hirabayashi J, Kuchroo VK, Yamauchi A, Hirashima M (2008) Galectin-9 increases Tim-3+ dendritic cells and CD8+ T cells and enhances antitumor immunity via galectin-9-Tim-3 interactions. J Immunol 181(11):7660–7669

    Article  CAS  PubMed  Google Scholar 

  50. Kadowaki T, Arikawa T, Shinonaga R, Oomizu S, Inagawa H, Soma G, Niki T, Hirashima M (2012) Galectin-9 signaling prolongs survival in murine lung-cancer by inducing macrophages to differentiate into plasmacytoid dendritic cell-like macrophages. Clin Immunol 142(3):296–307. https://doi.org/10.1016/j.clim.2011.11.006

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Professor Jean-François Michiels from the Central Anatomy Laboratory of Nice Pasteur University Hospital who provided expertise that greatly assisted the cytopathological examination of tumors.

Funding

This study was supported in part by the Centre Hospitalier Universitaire (CHU) de Nice (Appel à Projet Interne 2015), the Centre National de la Recherche Scientifique (CNRS) and the Institut National de la Santé et de la Recherche médicale (INSERM).

Author information

Author notes

  1. Annie Schmid-Alliana and Heidy Schmid-Antomarchi act as equivalent co-senior authors.

Authors and Affiliations

  1. Université Côte d’Azur, CNRS, Inserm, CHU Nice, iBV, Nice, France

    Julie Antomarchi, Damien Ambrosetti, Charlotte Cohen, Jérôme Delotte, Anne Chevallier, Babou Karimdjee-Soilihi, Mélanie Ngo-Mai, Annie Schmid-Alliana & Heidy Schmid-Antomarchi

  2. Pôle Santé St Jean, Cagnes/mer, France

    Babou Karimdjee-Soilihi

  3. iBV, Institut de Biologie Valrose, Univ Sophia Antipolis, Tour Pasteur, UFR Médecine, 28 Avenue de Valombrose, 06107, Nice cedex 2, France

    Heidy Schmid-Antomarchi

Authors
  1. Julie Antomarchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Damien Ambrosetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Charlotte Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jérôme Delotte
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne Chevallier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Babou Karimdjee-Soilihi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mélanie Ngo-Mai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Annie Schmid-Alliana
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Heidy Schmid-Antomarchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the experiments: Heidy Schmid-Antomarchi, Annie Schmid-Alliana.

Performed the experiments: Julie Antomarchi, Charlotte Cohen, Babou Karimdjee-Soilihi.

Analyzed the data: Julie Antomarchi, Charlotte Cohen, Annie Schmid-Alliana, Heidy Schmid-Antomarchi.

Contributed reagents/materials/analysis tools: Jérome Delotte, Anne Chevallier, Mélanie Ngo-Mai, Damien Ambrosetti.

Wrote the paper: Heidy Schmid-Antomarchi, Annie Schmid-Alliana, Julie Antomarchi, Charlotte Cohen .

Corresponding author

Correspondence to Heidy Schmid-Antomarchi.

Ethics declarations

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standarts.

For this study formal consent is not requiered.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 153 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Antomarchi, J., Ambrosetti, D., Cohen, C. et al. Immunosuppressive Tumor Microenvironment Status and Histological Grading of Endometrial Carcinoma. Cancer Microenvironment 12, 169–179 (2019). https://doi.org/10.1007/s12307-019-00225-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12307-019-00225-1

Keywords

Search

Navigation