M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F20%3A43920396" target="_blank" >RIV/00216208:11120/20:43920396 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/20:10413705 RIV/00216208:11150/20:10413705 RIV/00179906:_____/20:10413705 RIV/00064203:_____/20:10413705

Výsledek na webu

<a href="https://doi.org/10.1136/jitc-2020-000979" target="_blank" >https://doi.org/10.1136/jitc-2020-000979</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1136/jitc-2020-000979" target="_blank" >10.1136/jitc-2020-000979</a>

Jazyk výsledku

angličtina

Název v původním jazyce

M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer

Popis výsledku v původním jazyce

BACKGROUND: The immunological microenvironment of primary high-grade serous carcinomas (HGSCs) has a major impact on disease outcome. Conversely, little is known on the microenvironment of metastatic HGSCs and its potential influence on patient survival. Here, we explore the clinical relevance of the immunological configuration of HGSC metastases. METHODS: RNA sequencing was employed on 24 paired primary tumor microenvironment (P-TME) and metastatic tumor microenvironment (M-TME) chemotherapy-naive HGSC samples. Immunohistochemistry was used to evaluate infiltration by CD8(+) T cells, CD20(+) B cells, DC-LAMP(+) (lysosomal-associated membrane protein 3) dendritic cells (DCs), NKp46(+) (natural killer) cells and CD68(+)CD163(+) M2-like tumor-associated macrophages (TAMs), abundance of PD-1(+) (programmed cell death 1), LAG-3(+) (lymphocyte-activating gene 3) cells, and PD-L1 (programmed death ligand 1) expression in 80 samples. Flow cytometry was used for functional assessments on freshly resected HGSC samples. RESULTS: 1468 genes were differentially expressed in the P-TME versus M-TME of HGSCs, the latter displaying signatures of extracellular matrix remodeling and immune infiltration. M-TME infiltration by immune effector cells had little impact on patient survival. Accordingly, M-TME-infiltrating T cells were functionally impaired, but not upon checkpoint activation. Conversely, cytokine signaling in favor of M2-like TAMs activity appeared to underlie inhibited immunity in the M-TME and poor disease outcome. CONCLUSIONS: Immunosuppressive M2-like TAM infiltrating metastatic sites limit clinically relevant immune responses against HGSCs.

Název v anglickém jazyce

M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer

Popis výsledku anglicky

BACKGROUND: The immunological microenvironment of primary high-grade serous carcinomas (HGSCs) has a major impact on disease outcome. Conversely, little is known on the microenvironment of metastatic HGSCs and its potential influence on patient survival. Here, we explore the clinical relevance of the immunological configuration of HGSC metastases. METHODS: RNA sequencing was employed on 24 paired primary tumor microenvironment (P-TME) and metastatic tumor microenvironment (M-TME) chemotherapy-naive HGSC samples. Immunohistochemistry was used to evaluate infiltration by CD8(+) T cells, CD20(+) B cells, DC-LAMP(+) (lysosomal-associated membrane protein 3) dendritic cells (DCs), NKp46(+) (natural killer) cells and CD68(+)CD163(+) M2-like tumor-associated macrophages (TAMs), abundance of PD-1(+) (programmed cell death 1), LAG-3(+) (lymphocyte-activating gene 3) cells, and PD-L1 (programmed death ligand 1) expression in 80 samples. Flow cytometry was used for functional assessments on freshly resected HGSC samples. RESULTS: 1468 genes were differentially expressed in the P-TME versus M-TME of HGSCs, the latter displaying signatures of extracellular matrix remodeling and immune infiltration. M-TME infiltration by immune effector cells had little impact on patient survival. Accordingly, M-TME-infiltrating T cells were functionally impaired, but not upon checkpoint activation. Conversely, cytokine signaling in favor of M2-like TAMs activity appeared to underlie inhibited immunity in the M-TME and poor disease outcome. CONCLUSIONS: Immunosuppressive M2-like TAM infiltrating metastatic sites limit clinically relevant immune responses against HGSCs.

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

2020

Kód důvěrnosti údajů

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

Název periodika

Journal for ImmunoTherapy of Cancer

ISSN

2051-1426

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

"e000979"

Kód UT WoS článku

000564352500005

EID výsledku v databázi Scopus

2-s2.0-85089769957