TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer
| العنوان: | TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer |
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| المؤلفون: | Lorenzo Galluzzi, Jana Rakova, Ivan Praznovec, Roman Kodet, Kamila Hladíková, Lenka Kasikova, Eric Tartour, Ales Ryska, Jitka Fucikova, Ladislav Pecen, Petr Skapa, Iva Truxova, Michael J. Halaska, Radek Spisek, Anna Fialová, Michal Hensler, Josephine Pineau, Lucie Belicova, Alain Gey, Jan Laco, Tomas Brtnicky |
| المصدر: | Clinical Cancer Research. 25:4820-4831 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, Cancer Research, Serous carcinoma, CD8-Positive T-Lymphocytes, Carcinoma, Ovarian Epithelial, B7-H1 Antigen, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Immune system, Biomarkers, Tumor, Carcinoma, Humans, Medicine, Cytotoxic T cell, CTLA-4 Antigen, Hepatitis A Virus Cellular Receptor 2, Aged, Retrospective Studies, CD20, Tumor microenvironment, biology, business.industry, Lysosome-Associated Membrane Glycoproteins, Middle Aged, Prognosis, medicine.disease, Cystadenocarcinoma, Serous, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Survival Rate, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Female, business, Ovarian cancer, CD8 |
| الوصف: | Purpose: In multiple oncological settings, expression of the coinhibitory ligand PD-L1 by malignant cells and tumor infiltration by immune cells expressing coinhibitory receptors such as PD-1, CTLA4, LAG-3, or TIM-3 conveys prognostic or predictive information. Conversely, the impact of these features of the tumor microenvironment on disease outcome among high-grade serous carcinoma (HGSC) patients remains controversial. Experimental Design: We harnessed a retrospective cohort of 80 chemotherapy-naïve HGSC patients to investigate PD-L1 expression and tumor infiltration by CD8+ T cells, CD20+ B cells, DC-LAMP+ dendritic cells as well as by PD-1+, CTLA4+, LAG-3+, and TIM-3+ cells in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on a second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 308 HGSC samples was used as a confirmatory approach. Results: High levels of PD-L1 and high densities of PD-1+ cells in the microenvironment of HGSCs were strongly associated with an immune contexture characterized by a robust TH1 polarization and cytotoxic orientation that enabled superior clinical benefits. Moreover, PD-1+TIM-3+CD8+ T cells presented all features of functional exhaustion and correlated with poor disease outcome. However, although PD-L1 levels and tumor infiltration by TIM-3+ cells improved patient stratification based on the intratumoral abundance of CD8+ T cells, the amount of PD-1+ cells failed to do so. Conclusions: Our data indicate that PD-L1 and TIM-3 constitute prognostically relevant biomarkers of active and suppressed immune responses against HGSC, respectively. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6434b8dcc6cb2762aa26bf4a0468652bTest https://doi.org/10.1158/1078-0432.ccr-18-4175Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6434b8dcc6cb2762aa26bf4a0468652b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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