RT Journal Article
SR Electronic
T1 M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000979
DO 10.1136/jitc-2020-000979
VO 8
IS 2
A1 Michal Hensler
A1 Lenka Kasikova
A1 Karel Fiser
A1 Jana Rakova
A1 Petr Skapa
A1 Jan Laco
A1 Tereza Lanickova
A1 Ladislav Pecen
A1 Iva Truxova
A1 Sarka Vosahlikova
A1 Irena Moserova
A1 Ivan Praznovec
A1 Vit Drochytek
A1 Martina Rehackova
A1 Tomas Brtnicky
A1 Lukas Rob
A1 Vladimir Benes
A1 Jelena Pistolic
A1 Ludek Sojka
A1 Ales Ryska
A1 Catherine Sautes-Fridman
A1 Wolf Herve Fridman
A1 Lorenzo Galluzzi
A1 Radek Spisek
A1 Jitka Fucikova
YR 2020
UL http://jitc.bmj.com/content/8/2/e000979.abstract
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.