TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10395852" target="_blank" >RIV/00064203:_____/19:10395852 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/19:43918235 RIV/00216208:11130/19:10395852 RIV/00216208:11150/19:10395852 RIV/00179906:_____/19:10395852

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=GaBEW7Brqo" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=GaBEW7Brqo</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/1078-0432.CCR-18-4175" target="_blank" >10.1158/1078-0432.CCR-18-4175</a>

Jazyk výsledku

angličtina

Název v původním jazyce

TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer

Popis výsledku v původním jazyce

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-naive 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.

Název v anglickém jazyce

TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer

Popis výsledku anglicky

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-naive 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinical Cancer Research

ISSN

1078-0432

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

4820-4831

Kód UT WoS článku

000478021200025

EID výsledku v databázi Scopus

2-s2.0-85070088820