Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Immuno-Contexture and Immune Checkpoint Molecule Expression in Microsatellite Stable/Mismatch Repair Proficient Colorectal Carcinoma

Mauro Giacomelli
† ,
Matilde Monti
† ,
Diego Cesare Pezzola
† ,
Silvia Lonardi
ORCID logo ,
Mattia Bugatti
,
Francesco Missale
,
Rossella Cioncada
,
Laura Melocchi
ORCID logo ,
Viviana Giustini
,
Vincenzo Villanacci
,
Carla Baronchelli
,
Stefania Manenti
,
Luisa Imberti
ORCID logo ,
Emanuele Giurisato
† ORCID logo ,
William Vermi
*,† ORCID logo
†
These authors equally contributed.
Version 1 : Received: 6 May 2023 / Approved: 8 May 2023 / Online: 8 May 2023 (10:53:18 CEST)

A peer-reviewed article of this Preprint also exists.

Giacomelli, M.; Monti, M.; Pezzola, D.C.; Lonardi, S.; Bugatti, M.; Missale, F.; Cioncada, R.; Melocchi, L.; Giustini, V.; Villanacci, V.; Baronchelli, C.; Manenti, S.; Imberti, L.; Giurisato, E.; Vermi, W. Immuno-Contexture and Immune Checkpoint Molecule Expression in Mismatch Repair Proficient Colorectal Carcinoma. Cancers 2023, 15, 3097. Giacomelli, M.; Monti, M.; Pezzola, D.C.; Lonardi, S.; Bugatti, M.; Missale, F.; Cioncada, R.; Melocchi, L.; Giustini, V.; Villanacci, V.; Baronchelli, C.; Manenti, S.; Imberti, L.; Giurisato, E.; Vermi, W. Immuno-Contexture and Immune Checkpoint Molecule Expression in Mismatch Repair Proficient Colorectal Carcinoma. Cancers 2023, 15, 3097.

Abstract

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.

Keywords

Colorectal cancer; mismatch repair; microsatellite instability; immune checkpoint; double negative T cells; tumor microenvironment; T-cell exhaustion; interferon-γ; PD-L1

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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