TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.
PubMed
31076549
DOI
10.1158/1078-0432.ccr-18-4175
PII: 1078-0432.CCR-18-4175
Knihovny.cz E-zdroje
- MeSH
- antigen CTLA-4 imunologie metabolismus MeSH
- antigeny CD274 imunologie metabolismus MeSH
- buněčný receptor 2 viru hepatitidy A imunologie metabolismus MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- dospělí MeSH
- epiteliální ovariální karcinom imunologie metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny asociované s lyzozomy imunologie metabolismus MeSH
- míra přežití MeSH
- nádorové biomarkery imunologie metabolismus MeSH
- nádorové proteiny imunologie metabolismus MeSH
- prognóza MeSH
- regulace genové exprese u nádorů * MeSH
- retrospektivní studie MeSH
- senioři MeSH
- serózní cystadenokarcinom imunologie metabolismus patologie MeSH
- tumor infiltrující lymfocyty imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- antigen CTLA-4 MeSH
- antigeny CD274 MeSH
- buněčný receptor 2 viru hepatitidy A MeSH
- CD274 protein, human MeSH Prohlížeč
- CTLA4 protein, human MeSH Prohlížeč
- HAVCR2 protein, human MeSH Prohlížeč
- LAMP3 protein, human MeSH Prohlížeč
- membránové glykoproteiny asociované s lyzozomy MeSH
- nádorové biomarkery MeSH
- nádorové proteiny MeSH
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.
Department of Dermatology Yale School of Medicine New Haven Connecticut
Department of Radiation Oncology Weill Cornell Medical College New York New York
INSERM U970 Université Paris Descartes Sorbonne Paris Cité Paris France
Sandra and Edward Meyer Cancer Center New York New York
Service d'Immunologie Biologique AP HP Hopital Européen Georges Pompidou Paris France
Citace poskytuje Crossref.org
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