Biology subjects

Colombo, P.-E.

Publications and source records attributed to Colombo, P.-E..

3 recordsLinked to original sources

bioRxiv2026

Cancer-Associated Mesothelial Cells Drive Immune Escape and Therapy Resistance in Ovarian Cancer

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. CAMCSerpinb2+ cells have reduced expression of pro-inflammatory cytokines (IL-2, IL-7, IL-12, IL-15) and increased expression of IL-10, TGF{beta}1, and CCL17, promoting regulatory T cell recruitment and tolerogenic CD4+ T cell responses. Functionally, CAMCSerpinb2+ 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 O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/698232v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@14e9098org.highwire.dtl.DTLVardef@f6f929org.highwire.dtl.DTLVardef@601517org.highwire.dtl.DTLVardef@8cc7c_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Addressing multiple facets of ligand-receptor network inference including single-cell proteomics

Distinct ligand-receptor interaction (LRI) inference tools often produce markedly different results, and their performance can vary considerably across datasets. Indeed, performance is influenced by differences in experimental designs and dataset-specific features, making it difficult to establish a universal LRI tool. To address this challenge, we expanded our SingleCellSignalR Bioconductor package to provide an integrated framework that incorporates alternative scoring strategies and adjustable analytical depth. We motivate this choice through the analysis of two single-cell transcriptomics datasets that exemplify contrasting experimental designs. Leveraging the new framework flexibility, we present a detailed analysis of paired single-cell proteomics and transcriptomics data, providing, to our knowledge, the first direct comparison of LRI inference across these complementary modalities at single-cell resolution. Finally, we demonstrate how the same framework seamlessly accommodates additional underexplored data types from the LRI perspective, including patient-derived mouse xenografts and bulk RNA sequencing of upstream-sorted cell populations.

bioinformatics↗

bioRxiv2024

Deciphering the tumor-infiltrating CD73+ regulatory gammadelta T cell ecosystem associated with poor survival of patients with ovarian cancer

The ability of tumor cells to overcome immune surveillance is an essential step in tumor development and progression. Among the immune cells playing a role in tumor control, {gamma}{delta} T cells contribute to the immune response against many tumor types through their direct cytotoxic activity against cancer cells and their capacity to regulate the functions of other immune cells. However, their presence in the tumor microenvironment is also associated with poor prognosis, suggesting that {gamma}{delta} T cells may also have pro-tumor activities. We previously described a regulatory {gamma}{delta} T-cell subset that expresses CD73 and produces IL-10, IL-8 and adenosine. Here, we report a higher CD73+ {gamma}{delta} T cell density in the tumor microenvironment of ovarian cancer samples from patients with short-term than long-term survival. Starting from this original observation, we investigated their neighborhood and described a specific ecosystem according to their pro-tumor functions.

cancer biology↗