ARTICLE | doi:10.20944/preprints202305.0526.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Colorectal cancer; mismatch repair; microsatellite instability; immune checkpoint; double negative T cells; tumor microenvironment; T-cell exhaustion; interferon-γ; PD-L1
Online: 8 May 2023 (10:53:18 CEST)
CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.