Cancer-associated mesothelial cells drive immune escape and therapy resistance in ovarian cancer
Abstract
Cancer-associated mesothelial cells (CAMCs) are key modulators of the ovarian tumor microenvironment, contributing to tumor growth an immune evasion. Normal mesothelial cells play a role in peritoneal homeostasis and immune surveillance and represent the first point of contact during abdominal dissemination of ovarian cancers. Yet, their role in ovarian tumor immunity remains poorly understood. Here, we map the cellular states, spatial organization, and immune functions of CAMCs across ovarian cancer progression. Using lineage tracing and spatial transcriptomics, we demonstrate that CAMCs originate from mesothelial cells at the tumor surface and can progressively infiltrate the tumor core, undergoing a phenotypic transition towards fibroblast-like and immunosuppressive states. We characterize the function of an unrecognized CAMC subtype marked by SERPINB2 + expression, and a combination of markers absent in normal mesothelial cells. CAMC Serpinb2+ cells have reduced expression of pro-inflammatory cytokines (IL-2, IL-7, IL-12, IL-15) and increased expression of IL-10, TGFß1, and CCL17, promoting regulatory T cell recruitment and tolerogenic CD4 + T cell responses. Functionally, CAMC Serpinb2+ accelerate tumor growth, reduce CD4 + T and B cell infiltration, and expand Treg populations, ultimately leading to immunotherapy resistance. Together, our findings identify CAMCs as a potential therapeutic target in peritoneal carcinomatosis and as a means of restoring sensitivity to current treatments. Graphical abstract
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BibTeX
@article{chauvin2026cancerassociated,
title = {{Cancer-associated mesothelial cells drive immune escape and therapy resistance in ovarian cancer}},
author = {Maeva Chauvin and Julien Roche-Prellezo and Virginie Lafont and Henri-Alexandre Michaud and Estelle Tromelin and Robin Michel and Clara Freixinos and Marie-Charlotte Meinsohn and Pierre-Emmanuel Colombo and Nathalie Bonnefoy and Laurent Gros and David Pépin},
journal = {Journal for Immunotherapy of Cancer},
year = {2026},
month = jul,
doi = {10.1136/jitc-2026-015236},
url = {https://hal.science/hal-05779724v1},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Cancer-associated mesothelial cells drive immune escape and therapy resistance in ovarian cancer
AU - Maeva Chauvin
AU - Julien Roche-Prellezo
AU - Virginie Lafont
AU - Henri-Alexandre Michaud
AU - Estelle Tromelin
AU - Robin Michel
AU - Clara Freixinos
AU - Marie-Charlotte Meinsohn
AU - Pierre-Emmanuel Colombo
AU - Nathalie Bonnefoy
AU - Laurent Gros
AU - David Pépin
PY - 2026
DA - 2026/07/30
JO - Journal for Immunotherapy of Cancer
DO - 10.1136/jitc-2026-015236
UR - https://hal.science/hal-05779724v1
AB - Cancer-associated mesothelial cells (CAMCs) are key modulators of the ovarian tumor microenvironment, contributing to tumor growth an immune evasion. Normal mesothelial cells play a role in peritoneal homeostasis and immune surveillance and represent the first point of contact during abdominal dissemination of ovarian cancers. Yet, their role in ovarian tumor immunity remains poorly understood. Here, we map the cellular states, spatial organization, and immune functions of CAMCs across ovarian cancer progression. Using lineage tracing and spatial transcriptomics, we demonstrate that CAMCs originate from mesothelial cells at the tumor surface and can progressively infiltrate the tumor core, undergoing a phenotypic transition towards fibroblast-like and immunosuppressive states. We characterize the function of an unrecognized CAMC subtype marked by SERPINB2 + expression, and a combination of markers absent in normal mesothelial cells. CAMC Serpinb2+ cells have reduced expression of pro-inflammatory cytokines (IL-2, IL-7, IL-12, IL-15) and increased expression of IL-10, TGFß1, and CCL17, promoting regulatory T cell recruitment and tolerogenic CD4 + T cell responses. Functionally, CAMC Serpinb2+ accelerate tumor growth, reduce CD4 + T and B cell infiltration, and expand Treg populations, ultimately leading to immunotherapy resistance. Together, our findings identify CAMCs as a potential therapeutic target in peritoneal carcinomatosis and as a means of restoring sensitivity to current treatments. Graphical abstract
SN - 2051-1426
ER -