Biology subjects

Mayoux, M.

Publications and source records attributed to Mayoux, M..

3 recordsLinked to original sources

bioRxiv2025

RIPPLET: Mutation-Only Gene and Pathway Profiling for Precision Oncology

Clinical implementation of comprehensive genomic profiling, via whole-genome (WGS) or whole-exome sequencing (WES), is constrained by sparse mutation burdens and analytic pipelines reliant on matched transcriptomes. Currently, gene-centric analysis prevails, but overlooks the complex, multigene and pathway perturbations shaping tumor biology. We introduce RIPPLET, a DNA-only framework converting somatic variants into quantitative gene-impact scores and topology-aware pathway-perturbation profiles. By integrating tissue-specific protein-protein interaction networks with cohort-informed reweighting, RIPPLET prioritizes likely functionally relevant alterations. Applied across 33 TCGA cancer types, RIPPLET surpasses four state-of-the-art multi-omic driver-prioritization tools in recovering cancer type-specific drivers. In a cohort of metastatic cutaneous melanomas, it identifies pathway signatures that predict drug response, provide prognostic insight and distinguish immune-infiltration phenotypes without RNA data, independently validated on an in-house cohort. RIPPLET enables DNA-only inference of tumor-specific gene and pathway dysregulation, aligning with clinical sequencing workflows and offering a scalable precision-oncology strategy in transcriptome-limited settings.

bioinformatics↗

bioRxiv2025

Memory CD4 T cells orchestrate neoadjuvant-responsive niches in colorectal cancer liver metastases

Colorectal cancer frequently progresses to liver metastases (CRLM), a stage with limited treatment options and poor prognosis. Neoadjuvant chemotherapy is used to control tumor growth and enable resection, yet many patients fail to respond, and the mechanisms underlying this variability remain unclear. To identify determinants of treatment response, we profiled T cell states and their spatial organization in CRLM. We found that spatial arrangement and polarization of CD4 memory T cell networks determine treatment outcome. In responders, Th1-like CD4 memory T cells organized with effector-memory CD8 T cells and antigen-presenting cells (APCs) into therapy-responsive immune niches (TRINs) that support CD4-mediated APC licensing and local immune engagement. Non-responders lacked such immune architecture, exhibiting myeloid-rich regions dominated by circulating-like CD4 memory and regulatory T cells. CD4-driven TRINs thus emerge as key determinants of chemotherapy efficacy and provide a rationale for developing biomarkers and strategies that enhance CD4-APC-CD8 crosstalk within organized immune niches. Statement of significanceTh1-polarized CD4 memory T cells form therapy-responsive immune niches (TRINs) that orchestrate CD4, CD8, and APC function in colorectal cancer liver metastases, a clinically challenging and immunologically cold tumor type. TRINs define chemotherapy response and provide a mechanistic foundation for biomarker development and immunotherapy strategies designed to restore anti-tumor immunity.

immunology↗

bioRxiv2025

Mapping Leukocyte Dynamics during Neuroinflammation Identifies Meningeal Monocyte-Derived Macrophages as Drivers of Progressive Disease

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by increasing disability. The cellular and molecular drivers of clinical transition towards progressive disease are poorly understood. Here, we combine single-cell profiling technologies with genetic and pharmacological perturbations across the course of murine CNS inflammation to dissect the role of the local immune landscape in disease progression. We uncover a chronic monocyte-to-phagocyte transition as a hallmark of progressive disease, characterized by the emergence of maladaptive, lipid-associated macrophages (LAMs) marked by lysosomal activation and fibrotic features. Spatial transcriptomics and multiplexed imaging revealed that these LAMs localized to the leptomeninges in close proximity to parenchymal colony-stimulating factor (CSF)-1 producing disease-associated microglia (DAMs) and meningeal granulocyte-macrophage (GM)-CSF-expressing T helper cells that license their differentiation. Interference with this local cytokine network revealed a protective role for resident microglia and implicated monocyte-derived phagocytes as key drivers of progressive neuroinflammation. Notably, LAM-like macrophages could also be identified in the meninges of people with MS, indicating a homology to human disease. By elucidating their ontogeny, spatial niche, and regulatory cytokine milieu, we provide a mechanistic framework for targeting harmful myeloid states while preserving reparative CNS immunity in progressive MS.

immunology↗