Biology subjects

Hemon, P.

Publications and source records attributed to Hemon, P..

4 recordsLinked to original sources

bioRxiv2026

AltraFlowSOM: A Semi-Supervised Framework for Imaging Mass Cytometry Phenotyping

Imaging Mass Cytometry (IMC) enables the simultaneous quantification of 40+ protein markers at single cell resolution in tissue, however biologically faithful phenotyping at scale remains a critical bottleneck. Unsupervised clustering fragments coherent populations or conversely merges biologically incoherent ones into a single cluster, supervised classifiers impose a closed vocabulary, and the presence of rare subsets (encoding clinically relevant biology) in conjunction with abundant subsets may be detrimental to detection performances. We present AltraFlowSOM, a semi-supervised extension of FlowSOM that embeds partial expert annotations directly into self-organizing map training via a two-layer SuperSOM architecture, balancing label-guided topology anchoring with unsupervised discovery. By anchoring the map to biologically labelled reference points, AltraFlowSOM circumvents the canonical dependency between batch correction and clustering. Evaluated under Leave-one-out cross validation on two independent IMC cohorts, Lupus Nephritis (n=22 ROIs) and Sjogren syndrome (n=10 ROIs), AltraFlowSOM outperformed all unsupervised and supervised baseline on Adjusted Rand Index, F1 scores (macro and weighted), weighted purity and in the identification of rare populations. The median Treg cell recovery exceeded that of all comparator methods. AltraFlowSOM resolves the scalability-alignment-discovery trilemma, by establishing a semi-supervised SOM as a generalizable method for high dimensional IMC phenotyping.

bioinformatics↗

bioRxiv2024

B-Cell Involvement in Immune Checkpoint Inhibitor-Induced Lichen Planus: A Comparative Analysis with Non-Drug-Related Lichen Planus.

BackgroundImmune checkpoint inhibitors (ICI) have significantly improved cancer prognosis but can lead to immune-related adverse events (irAE), including cutaneous manifestations affecting 30% to 60% of ICI-treated patients. However, the physiopathology of cutaneaous irAE remains unclear. ObjectiveThis study investigated the immune infiltration in tissues affected by cutaneous irAE to elucidate their contribution to the pathogenesis of these toxicities. MethodsSkin biopsies from 6 patients with ICI-induced lichenoid eruptions were compared using imaging mass cytometry to samples from 7 controls with non-drug-related lichen planus. ResultsT cells were the predominant cell type within the inflammatory infiltrate in all samples, but we observed a reduced T-cell infiltration and an increased B-cell frequency in ICI-induced lichen planus compared to non-drug related lichen planus. Among B cells, we observed a significant decrease in IgD-CD27-double-negative B cells and an increase in IgD+CD27-naive B cells. Spatial analysis demonstrated that infiltrating B cells were organized in aggregates close to T cells in ICI-induced lichen planus. LimitationsThis is a retrospective single-center study with a relatively small sample size. ConclusionThis study sheds light on the involvement of B cells in the pathogenesis of ICI-induced lichen planus, suggesting distinct immunological mechanisms from non-drug-related lichen planus. CAPSULE SUMMARYO_LILichenoid manifestations are a common but understudied side effect occurring in patients receiving anti-PD-1 antibodies. C_LIO_LIICI-induced lichen planus displays distinct physiopathology from non-drug-related lichen planus, with a decrease of T-cell infiltration concomitantly to the increase of B cells organized in aggregates. C_LI

immunology↗

bioRxiv2022

Deciphering the maturation of tertiary lymphoid structures in cancer and inflammatory diseases of the digestive tract using imaging mass cytometry: from high-level data to a simple architectural and functional grading

ObjectivePersistent inflammation can promote the development of tertiary lymphoid structures (TLS) within tissues resembling the secondary lymphoid organs (SLO) as lymph nodes (LN). The composition of the TLS across different organs and diseases could be of pathophysiological and medical interest. In this work, we compared TLS to SLO and between cancer and inflammatory diseases of the digestive tract. DesignColorectal and gastric tissues with different inflammatory diseases and cancers from the department of pathology of CHU Brest were analyzed based on 39 markers using imaging mass cytometry (IMC). Unsupervised and supervised clustering analyses of IMC images were used to compare SLO and TLS. ResultsUnsupervised analyses tended to group TLS per patient but not per disease. Supervised analyses of IMC images revealed that LN had a more organized structure than TLS and non-encapsulated SLO Peyers patches. TLS followed a maturation spectrum with close correlations between germinal cell (GC) markers evolution. The correlations between organizational and functional markers made relevant the previously proposed TLS division into three stages: lymphoid-aggregates (LA) (CD20+CD21-CD23-) had neither organization nor GC functionality, non-GC TLS (CD20+CD21+CD23-) were organized but lacked GCs functionality and GC-like TLS (CD20+CD21+CD23+) had GCs organization and functionality. This architectural and functional maturation grading of TLS pointed to differences across diseases. ConclusionTLS architectural and functional maturation grading is accessible with few markers allowing future diagnostic, prognostic, and predictive studies on the value of TLS grading, quantification and location within pathological tissues in cancers and inflammatory diseases. KEY MESSAGES- What is already known on this topic: Tertiary lymphoid structures (TLS) arise in organs under various pathological conditions and can be of prognostic significance. - What this study adds: This study deciphers the composition of TLS in digestive cancers and inflammatory diseases using massively multiplexed (39 markers) imaging mass cytometry (IMC). Beyond the term TLS, this study points to the heterogeneity of these structures in terms of composition and maturation but also the relevance of a simple architectural and functional three-stage grading of TLS. - How this study might affect research, practice, or policy: This preliminary study paves the way for future studies evaluating the diagnostic, prognostic and theranostic values of TLS maturation grading, quantification and location within tissues as novel biomarkers in inflammatory diseases and cancers.

immunology↗

bioRxiv2021

IL-21 and IFN-α have both opposite and redundant role on human innate precursors and memory B-cell differentiation.

Immunological memory is essential for effective immune protection upon antigen rechallenge. Memory B cells encompass multiple subsets, heterogeneous in terms of phenotypes, origins and precursors, anatomical localization, and functional responses. B-cell responses are conditioned by micro-environmental signals, including cytokines. Here, we analyzed in vitro the effects of two cytokines implicated in B-cell differentiation, interferon-alpha (IFN-) and interleukin (IL)-21, on the early functional response of four different mature B-cell subsets (IgD- CD27- naive, IgD+ CD27+ unswitched, IgD- CD27+ switched and double-negative B cells). The dual response of naive and memory B cells to IL-21 allowed us to uncover a unique IgD+ CD27- CD10- B-cell population (referred to as NARB+) characterized by the expression of marginal zone B-cell markers CD45RB and CD1c. Similar to memory B cells, NARB+ cells were in a pre-activated state, allowing them to rapidly differentiate into plasmablasts upon innate signals while maintaining their susceptibility to IL-21 activation-induced apoptosis as observed for the naive compartment. Both in-depth phenotypic analysis of circulating B cells, and identification of these cells in spleen, tonsil and gut-associated lymphoid tissues, supported that NARB+ are uncommitted precursors of human marginal zone B cells.

immunology↗