Biology subjects

Chauvin, M.

Publications and source records attributed to Chauvin, M..

6 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↗

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↗

bioRxiv2024

FSTL3 is a biomarker of poor prognosis and is associated with immunotherapy resistance in ovarian cancer.

High-grade serous ovarian carcinoma (HGSOC), is associated with high mortality rates due to late-stage diagnosis and limited treatment options. We investigated the role of FSTL3 in ovarian cancer progression both as a prognostic biomarker and as a potential therapeutic target. We measured levels of follistatin (FST) and follistatin-like 3 (FSTL3) in 96 ovarian cancer patient ascites samples and found that FSTL3 overexpression was more predominant than FST and associated with poorer survival outcomes. Mice implanted with an HGSOC syngeneic cell line bearing common alterations in ovarian cancer (KRASG12V, P53R172H, CCNE1oe, AKT2oe) had increasing levels of FST and FSTL3 in serum during tumor growth. Further alteration of this model to generate a knockout of FST (KPCA.FSTKO) and an overexpression of human FSTL3 (KPCA.FSTKO_hFSTL3), revealed that FSTL3 expression was associated with a more fibrotic tumor microenvironment, correlating with an increased abundance of cancer-associated myofibroblasts (myCAFs), and cancer cells with a more mesenchymal phenotype. Tumors overexpressing FSTL3 had less immunocyte infiltration and a significantly reduced intratumoral T-cell abundance (CD4+, CD8+). FSTL3 overexpression completely abrogated tumor response to PPC treatment (Prexasertib combined with PD-1 and CTLA-4 blockade) compared to controls, suggesting that FSTL3 may be involved in immunotherapy resistance. In conclusion, this study suggests a role for FSTL3 as a prognostic marker and as therapeutic target in HGSOC, where it may play a role in promoting a mesenchymal tumor phenotype, maintaining an immunosuppressive tumor microenvironment, and driving immunotherapy resistance. HighlightsHigh FSTL3 levels are associated with poor outcomes in ovarian cancer. Serum levels of FSTL3 increase during tumor growth and reflect tumor burden and therapy response. Overexpression of FSTL3 in cancer cells promotes a fibrotic tumor microenvironment and immunocyte exclusion. Overexpression of FSTL3 in tumors induces resistance to Chk1 and immune checkpoint inhibitor combination therapy. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/627747v1_ufig1.gif" ALT="Figure 1000"> View larger version (45K): org.highwire.dtl.DTLVardef@16d0608org.highwire.dtl.DTLVardef@a70028org.highwire.dtl.DTLVardef@1fb4895org.highwire.dtl.DTLVardef@5a42b4_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

AMH protects the ovary from doxorubicin by regulating cell fate and the response to DNA damage

Anti-Mullerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, the mechanisms of DOX toxicity and AMH rescue in the ovary remain unclear. Herein, we characterize these mechanisms in various ovarian cell types using scRNAseq. In the mesenchyme, DOX activates the intrinsic apoptotic signaling pathway through p53 class mediators, particularly affecting theca progenitors, while co-treament with AMH halts theca differentiation and reduces apoptotic gene expression. In preantral granulosa cells, DOX upregulates the cell cycle inhibitor Cdkn1a and dysregulates Wnt signaling, which are ameliorated by AMH co-treatment. Finally, in follicles, AMH induces Id3, a protein involved in DNA repair, which is necessary to prevent the accumulation of DNA lesions marked by {gamma}-H2AX in granulosa cells. Altogether this study characterizes cell, and follicle stage-specific mechanisms of AMH protection of the ovary, offering promising new avenues for fertility preservation in cancer patients undergoing chemotherapy. HighlightsO_LIDoxorubicin treatment induces DNA damage that activates the p53 pathway in stromal and follicular cells of the ovary. C_LIO_LIAMH inhibits the proliferation and differentiation of theca and granulosa cells and promotes follicle survival following Doxorubicin insult. C_LIO_LIAMH treatment mitigates Doxorubicin-induced DNA damage in the ovary by preventing the accumulation of {gamma}-H2AX-positive unresolved foci, through increased expression of ID3, a protein involved in DNA repair. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/595356v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@19f6752org.highwire.dtl.DTLVardef@383e74org.highwire.dtl.DTLVardef@8c38f7org.highwire.dtl.DTLVardef@1efe797_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

A single cell atlas of the cycling murine ovary

The estrous cycle is regulated by rhythmic endocrine interactions of the nervous and reproductive systems, which coordinate the hormonal and ovulatory functions of the ovary. Folliculogenesis and follicle progression require the orchestrated response of a variety of cell types to allow the maturation of the follicle and its sequela, ovulation, corpus luteum (CL) formation, and ovulatory wound repair. Little is known about the cell state dynamics of the ovary during the estrous cycle, and the paracrine factors that help coordinate this process. Herein we used single-cell RNA sequencing to evaluate the transcriptome of > 34,000 cells of the adult mouse ovary and describe the transcriptional changes that occur across the normal estrous cycle and other reproductive states to build a comprehensive dynamic atlas of murine ovarian cell types and states.

developmental biology↗

bioRxiv2021

Sexually dimorphic placental responses to maternal SARS-CoV-2 infection

There is a persistent male bias in the prevalence and severity of COVID-19 disease. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of disease in adults, and play a key role in the placental anti-viral response. Moreover, the interferon response has been shown to alter Fc-receptor expression, and therefore may impact placental antibody transfer. Here we examined the intersection of viral-induced placental interferon responses, maternal-fetal antibody transfer, and fetal sex. Placental interferon stimulated genes (ISGs), Fc-receptor expression, and SARS-CoV-2 antibody transfer were interrogated in 68 pregnancies. Sexually dimorphic placental expression of ISGs, interleukin-10, and Fc receptors was observed following maternal SARS-CoV-2 infection, with upregulation in males. Reduced maternal SARS-CoV-2-specific antibody titers and impaired placental antibody transfer were noted in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

immunology↗