PT - JOURNAL ARTICLE AU - Michal Hensler AU - Lenka Kasikova AU - Karel Fiser AU - Jana Rakova AU - Petr Skapa AU - Jan Laco AU - Tereza Lanickova AU - Ladislav Pecen AU - Iva Truxova AU - Sarka Vosahlikova AU - Irena Moserova AU - Ivan Praznovec AU - Vit Drochytek AU - Martina Rehackova AU - Tomas Brtnicky AU - Lukas Rob AU - Vladimir Benes AU - Jelena Pistolic AU - Ludek Sojka AU - Ales Ryska AU - Catherine Sautes-Fridman AU - Wolf Herve Fridman AU - Lorenzo Galluzzi AU - Radek Spisek AU - Jitka Fucikova TI - M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer AID - 10.1136/jitc-2020-000979 DP - 2020 Aug 01 TA - Journal for ImmunoTherapy of Cancer PG - e000979 VI - 8 IP - 2 4099 - http://jitc.bmj.com/content/8/2/e000979.short 4100 - http://jitc.bmj.com/content/8/2/e000979.full SO - J Immunother Cancer2020 Aug 01; 8 AB - 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.