Patrice Hemon

• Doctor of Philosophy
• Engineer at French Institute of Health and Medical Research

This study aimed to evaluate the predictive value of MHC class II (MHC-II) expression by melanoma cells in a large cohort of metastatic cutaneous melanoma patients treated with immune checkpoint inhibitors (ICIs). We conducted a single-center, retrospective study involving stage IV cutaneous melanoma patients who received ICI as first-line therapy....

Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies,...

In the realm of inflammation, including conditions like cancers, infections, and autoimmune diseases, the emergence of tertiary lymphoid structures (TLS) holds significant implications for prognosis and treatment response. Yet, traditional methodologies such as immunohistochemistry and immunofluorescence falter in capturing the nuanced complexities...

Objective Tissue-resident memory cells (Trm) are a subset of T cells residing persistently and long-term within specific tissues that contribute to persistent inflammation and tissue damage. We characterised the phenotype and function of Trm and the role of CD103 in primary Sjogren’s syndrome (pSS). Methods In both pSS and non-pSS sicca syndrome p...

Imaging mass cytometry (IMC) is a metal mass spectrometry-based method allowing highly multiplex immunophenotyping of cells within tissue samples. However, some limitations of IMC are its 1-µm resolution and its time and costs of analysis limiting respectively the detailed histopathological analysis of IMC-produced images and its application to sma...

Since the advent of anti-PD1 immune checkpoint inhibitor (ICI) immunotherapy, cutaneous melanoma has undergone a true revolution with prolonged survival, as available 5-year updates for progression-free survival and overall survival demonstrate a durable clinical benefit for melanoma patients receiving ICI. However, almost half of patients fail to...

Background: Immune 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. Objective: This study investigated the immune infiltration...

Persistent inflammation can promote the development of tertiary lymphoid structures (TLS) within tissues resembling secondary lymphoid organs (SLO) such as lymph nodes (LN). The composition of TLS across different organs and diseases could be of pathophysiological and medical interest. In this work, we compared TLS to SLO in cancers of the digestiv...

The recent emergence of imaging mass cytometry technology has led to the generation of an increasing amount of high-dimensional data and, with it, the need for suitable performant bioinformatics tools dedicated to specific multiparametric studies. The first and most important step in treating the acquired images is the ability to perform highly eff...

Objective: Persistent 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...

Imaging mass cytometry (IMC) enables the in situ analysis of in-depth-phenotyped cells in their native microenvironment within the preserved architecture of a single tissue section. To date, it permits the simultaneous analysis of up to 50 different protein- markers targeted by metal-conjugated antibodies. The application of IMC in the field of can...

The integrative analysis of tumor immune microenvironment (TiME) components, their interactions and their microanatomical distribution is mandatory to better understand tumor progression. Imaging Mass Cytometry (IMC) is a high dimensional tissue imaging system which allows the comprehensive and multiparametric in situ exploration of tumor microenvi...

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 analyze...

Background Dysregulation in calcium (Ca²⁺) signaling is a hallmark of chronic lymphocytic leukemia (CLL). While the role of the B cell receptor (BCR) Ca²⁺ pathway has been associated with disease progression, the importance of the newly described constitutive Ca²⁺ entry (CE) pathway is less clear. In addition, we hypothesized that these differences...

Calcium (Ca2+ ) signaling controls T-cell activation and functions. Ca2+ concentrations are locally detected and controlled by Ca2+ -sensors (STIM1 and 2 detecting the depletion from ER stores channels) and Ca2+ -channels (ORAI1-3 in the cell membrane and VDAC1 in the outer mitochondrial membrane). We first validated and titrated antibodies to asse...

Biases in the distribution and phenotype of T, B, and antigen-presenting cell populations are strongly connected to mechanisms of disease development in mouse models of systemic lupus erythematosus (SLE). Here, we describe longitudinal changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and spleen from two lupus-prone stra...

Maintenance of self-tolerance of auto-reactive lymphocytes is a fundamental mechanism to prevent the onset of autoimmune diseases. Deciphering the mechanisms involved in the deregulations leading to tolerance disruption and autoimmunity is still a major area of interest to identify new therapeutic targets and options. Ca(2+) signaling plays a major...

CXCR4 plays a central role in B cell immune response, notably by promoting plasma cell (PC) migration and maintenance in the bone marrow (BM). Gain-of-function mutations in CXCR4 affecting receptor desensitization have been reported in the rare immunodeficiency called WHIM syndrome (WS). Despite lymphopenia, patients mount an immune response but fa...

Our knowledge and control of the pathogenesis induced by the filariae remain limited due to experimental obstacles presented by parasitic nematode biology and the lack of selective prophylactic or curative drugs. Here we thought to investigate the role of neutrophils in the host innate immune response to the infection caused by the Litomosoides sig...

Blood neutrophils number in the 6 hours following infection. Total numbers of neutrophils (millions of cells per mL of blood) before (H0) and after SC infection (2 and 6 hours, H2 and H6) with 40 infective larvae of wt (white bars) and Cxcr4+/1013 (black bars) mice. Results are expressed as mean +/- SEM. T-tests *: p < 0.05, ns = not significant. (...

Visualization of NET-like structures in the skin of mutant mice 6 hours following infection. Images captured from scanned skin sections from mutant mice (+/1013) and their normal littermate (wt) that were collected from the inoculation site 6 hours after infection (Inf) or injection of RPMI media (Ctrl). Two skin sections are shown (A and B) for ea...

A model of L. sigmodontis filarial infection in mice: Time course and invasion routes. Recovery rate in pleural cavity (% of inoculum, in green) and total PleCs (X106 cells, in blue) in resistant and susceptible mice in the course of the filarial infection adapted from [4, 39, 47, 77–79]. Hypothetical location and migration path of the parasite upo...

Blood number of neutrophils the first 5 days following infection. Total numbers of blood neutrophils (millions of cells per mL of blood) measured every day the first 5 days following SC injection of 40 infective larvae in wt and Cxcr4+/1013 mice (n = 5). Means were compared at each time point for each mice, t-tests, ***: p < 0.001. (TIF)

Parasitic success is dramatically reduced in Cxcr4+/1013 mutant mice as early as day 8 post infection. L. sigmodontis (40 larvae) were subcutaneously injected into wt and Cxcr4+/1013 C57BL/6 mice. Worms were harvested in the pleural cavity of the mice 8 days p.i. and counted (nF). Results are expressed as mean +/- SEM, n = 5 mice per group, MW-test...

Cxcr4+/1013 neutrophils exhibit a gain of Cxcr4-dependent chemotaxis. A: Chemotaxis of murine BM-derived neutrophils from wt and Cxcr4+/1013 control mice and their infected counterparts (at 20 days p.i) in response to Cxcl1 (50nM), Cxcl12 (10nM) or Cxcl12 (10nM) + AMD3100 (200μM). Migrating neutrophils recovered in the lower chamber were gated as L...

Total number of PleCs and their composition. A: Cells were harvested and counted at necropsy at 20 days p.i. upon flushing the pleural cavity of non-infected (wt ctrl and +/1013 ctrl) and infected (wt inf and +/1013 inf) mice. Cells were then stained with F4/80-APC, Siglec-F-PE, Ly6G-FITC, CD3-PE and B220-FITC directed antibodies. B: Gating strateg...

Steady state levels and recruitment of cells in the skin upon filariae inoculation. Skin sections were collected before inoculation (control mice, Ctrl) or excised from the inoculation site 6 hours p.i. (Infected mice, Inf), embedded in paraffin and stained with H&E for the visualization of eosinophils (A), anti-F4/80 for macrophages (B) or toluidi...

Cxcl12 levels in dermal stroma of wt and mutant Cxcr4+/1013 mice at steady state and 6 hours following infection. Images captured from scanned skin sections from mutant mice and their wt littermate that were collected from the inoculation site 6 hours after infection (Infected H6 p.i.) or injection of RPMI media (untreated). Skin sections were embe...

Blood number of neutrophils throughout the course of filarial infection (Days 1–40) following IV or SC challenges. Raw blood neutrophils counts from the experiments presented in Fig 2 panel C. Neutrophil counts (millions of cells per mL of blood) were obtained from mice either IV inoculated with 40 infective larvae (IV L3 wt and IV L3 +/1013, n = 5...

Background & aim: Kupffer cells (KC) play a key role in the onset of inflammation in non-alcoholic steatohepatitis (NASH). The glucocorticoid receptor (GR) induces glucocorticoid-induced leucine zipper (GILZ) expression in monocytes/macrophages and is involved in several inflammatory processes. We hypothesized that the GR-GILZ axis in KC may contr...

Human papillomavirus (HPV) infection is estimated to be the causal agent in 5% of all human cancers and is the leading cause of genital warts, which is the most common sexually transmitted viral disease. Currently, there are no medications to treat HPV infection, and therapeutic strategies primarily target HPV-related cancer rather than viral infec...

Ca2+ signaling is a key regulator of B lymphocyte cell fate and defects in this signaling pathway have been reported in numerous diseases such as Chronic lymphocytic leukemia (CLL). CLL is a B cell clonal disorder characterized by the accumulation of mature monoclonal CD5+ B cells. Although CLL could be considered to be a proliferative disease, mos...

Filariases are chronic diseases affecting 200 million people worldwide. Despite considerable effort to reduce disease burden, filarial infections remain a major public health problem requiring new therapeutic approaches. In our study, we used Litomosoides sigmodontis as a well-established murine model of filarial infections. We have previously show...

Filariases are chronic diseases affecting 200 million people worldwide. Despite considerable effort to reduce disease burden, particularly through mass drug administration programs, filarial infections remain a major public health problem requiring new therapeutic approaches. In our study, we used Litomosoides sigmodontis as a well-established muri...

The ectonucleotidases CD39 and CD73 hydrolyze extracellular ATP and ADP to generate adenosine, which binds to adenosine receptors and inhibits T cell and NK cell responses, thereby suppressing the immune system. The generation of adenosine via the CD39/CD73 pathway is recognized as a major mechanism of Treg immunosuppressive function. The number of...

Homing of inflammatory cells to the liver is key in the progression of non-alcoholic steatohepatitis (NASH). An abnormal response of CD4+ T cells from obese mice to the chemotactic effect of CXCL12 has been reported but the mechanism involved in this process and relevance in patients are unknown. We aimed to explore the mechanism involved in the ab...

Les filarioses (filarioses lymphatiques, onchocercose, loase) sont des maladies chroniques affectant 200 millions de personnes dans le monde. Malgré des efforts considérables pour limiter leur impact, le développement de résistances aux traitements et l'absence de macrofilaricides justifient la recherche de nouvelles approches thérapeutiques. C’est...

Systemic lupus erythematosus is a chronic inflammatory autoimmune disease, the development of which is characterized by a progressive loss of renal function. Such dysfunction is associated with leukocyte infiltration in the glomerular and tubulointerstitial compartments in both human and experimental lupus nephritis. In this study, we investigated...

Allergic contact dermatitis (ACD) is induced by low molecular weight electrophilic chemicals and metal ions. Chemical contact sensitizers trigger reactive oxygen species (ROS) production and provoke electrophilic stress leading to the accumulation of the transcription factor nuclear related factor 2 (Nrf2) in innate immune cell types. The objective...

Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral...

Melanoma is the most aggressive skin cancer in humans that often expresses MHC class II (MHC II) molecules, which could make these tumors eliminable by the immune system. However, this MHC II expression has been associated with poor prognosis, and there is a lack of immune-mediated eradication. The lymphocyte activation gene-3 (LAG-3) is a natural...

Organ transplantation represents a unique therapeutic option for irreparable organ dysfunction and rejection of transplants results from a breakdown in operational tolerance. Although endothelial cells (ECs) are the first target in graft rejection following kidney transplantation, their capacity to alloactivate and generate particular T lymphocyte...