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M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer
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SYSNO ASEP 0531917 Document Type J - Journal Article R&D Document Type The record was not marked in the RIV Subsidiary J Ostatní články Title M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer Author(s) Hensler, M. (CZ)
Kašíková, L. (CZ)
Fišer, K. (CZ)
Raková, J. (CZ)
Skapa, P. (CZ)
Laco, J. (CZ)
Láníčková, T. (CZ)
Pecen, Ladislav (UIVT-O) RID, SAI, ORCID
Truxová, I. (CZ)
Vošahlíková, Š. (CZ)
Moserová, I. (CZ)
Práznovec, I. (CZ)
Drochýtek V. (CZ)
Řeháčková M. (CZ)
Brtnický, T. (CZ)
Rob, L. (CZ)
Beneš, V. (DE)
Pistolic, J. (DE)
Sojka, L. (CZ)
Ryška, A. (CZ)
Sautes-Fridman, C. (FR)
Fridman, W. H. (FR)
Galluzzi, L. (US)
Špíšek, R. (CZ)
Fučíková, J. (CZ)Article number e000979 Source Title Journal for ImmunoTherapy of Cancer
Roč. 8 (2020)Number of pages 12 s. Language eng - English Country GB - United Kingdom Method of publishing Open access DOI 10.1136/jitc-2020-000979 Annotation 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. Workplace Institute of Computer Science Contact Tereza Šírová, sirova@cs.cas.cz, Tel.: 266 053 800 Year of Publishing 2021
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