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M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer
M. Hensler, L. Kasikova, K. Fiser, J. Rakova, P. Skapa, J. Laco, T. Lanickova, L. Pecen, I. Truxova, S. Vosahlikova, I. Moserova, I. Praznovec, V. Drochytek, M. Rehackova, T. Brtnicky, L. Rob, V. Benes, J. Pistolic, L. Sojka, A. Ryska, C....
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.
NLK
BioMedCentral Open Access
od 2013
Directory of Open Access Journals
od 2013
Free Medical Journals
od 2013
PubMed Central
od 2013
Europe PubMed Central
od 2013
ProQuest Central
od 2013-05-01
Open Access Digital Library
od 2013-01-01
Open Access Digital Library
od 2013-01-01
Health & Medicine (ProQuest)
od 2013-05-01
ROAD: Directory of Open Access Scholarly Resources
od 2013
PubMed
32819974
DOI
10.1136/jitc-2020-000979
Knihovny.cz E-zdroje
- MeSH
- imunosupresivní léčba metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy imunologie MeSH
- metastázy nádorů MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové mikroprostředí MeSH
- nádory vaječníků imunologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let 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
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.
Caryl and Israel Englander Institute for Precision Medicine New York City New York USA
Department of Dermatology Yale University School of Medicine New Haven Connecticut USA
Department of Radiation Oncology Weill Cornell Medical College New York City New York USA
Genomics Core Facility EMBL Heidelberg Germany
INSERM U1138 Centre de Recherche des Cordeliers Paris France
Sandra and Edward Meyer Cancer Center New York City New York USA
Citace poskytuje Crossref.org
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- $a 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.
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