TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11120/19:43918235 RIV/00216208:11130/19:10395852 RIV/00216208:11150/19:10395852 RIV/00179906:_____/19:10395852
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Clinical Cancer Research
ISSN
1078-0432
e-ISSN
—
Volume of the periodical
25
Issue of the periodical within the volume
15
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
4820-4831
UT code for WoS article
000478021200025
EID of the result in the Scopus database
2-s2.0-85070088820