M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11130/20:10413705 RIV/00216208:11150/20:10413705 RIV/00179906:_____/20:10413705 RIV/00064203:_____/20:10413705
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal for ImmunoTherapy of Cancer
ISSN
2051-1426
e-ISSN
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Volume of the periodical
8
Issue of the periodical within the volume
2
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
"e000979"
UT code for WoS article
000564352500005
EID of the result in the Scopus database
2-s2.0-85089769957