Raphaël Mattiuz
A5001830941- Gut microbiota and health
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- T-cell and B-cell Immunology
- Phagocytosis and Immune Regulation
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- IL-33, ST2, and ILC Pathways
- Acute Myeloid Leukemia Research
- Genomics and Chromatin Dynamics
- Histone Deacetylase Inhibitors Research
- Immune responses and vaccinations
- Silicon Carbide Semiconductor Technologies
- Cytokine Signaling Pathways and Interactions
- Reproductive System and Pregnancy
- Single-cell and spatial transcriptomics
- Genetic factors in colorectal cancer
- Gene expression and cancer classification
- Mycobacterium research and diagnosis
- Immune Response and Inflammation
Icahn School of Medicine at Mount Sinai
2021-2025
Tisch Hospital
2023-2024
Tisch Cancer Institute
2023
Centre d’Immunologie de Marseille-Luminy
2018-2021
Babraham Institute
2018-2021
Inserm
2020
Centre National de la Recherche Scientifique
2020
Institut Cochin
2017
Abstract The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize in intestinal epithelia find that H3 at lysine 18 is a surprisingly abundant the small intestine crypt colon, linked show this highly dynamic regulated during cell cycle. identify class I deacetylases, HDAC1, HDAC2, HDAC3, as major executors of decrotonylation. known HDAC...
Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. In this study, we establish that of the immune system, regardless age stroma and tumor, drives lung cancer progression. Hematopoietic enhances emergency myelopoiesis, resulting in local accumulation myeloid progenitor–like cells tumors. These are source interleukin (IL)–1⍺, which enhanced response. The age-associated decline DNA methyltransferase 3A IL-1⍺ production, disrupting IL-1 receptor 1...
Abstract Objectives To better understand how immune responses may be harnessed against breast cancer, we investigated which cell types and signalling pathways are required for spontaneous control of a mouse model mammary adenocarcinoma. Methods The NOP23 adenocarcinoma line expressing epitopes derived from the ovalbumin antigen is spontaneously controlled when orthotopically engrafted in syngeneic C57BL/6 mice. We combined this cancer with antibody‐mediated depletion lymphocytes mutant mice...
Myeloid cells represent a dominant cellular compartment of tumor lesions and play key roles in inception, progression, metastasis, response to treatment. Mononuclear phagocytes (MNPs), which include dendritic macrophages, are unique among myeloid cells, as they not only shape both the broader composition state microenvironment but can also specifically instruct cancer-specific, T cell–mediated cell killing, making them especially attractive targets for cancer Although MNPs remain difficult...
Type 1 conventional DCs (cDC1) excel in the cross-priming of CD8+ T cells, which is crucial for orchestrating efficient immune responses against viruses or tumors. However, our understanding their physiological functions and molecular regulation has been limited by lack proper mutant mouse models allowing conditional genetic targeting. Because Xcr1 A530099j19rik (Karma/Gpr141b) genes belong to core transcriptomic fingerprint cDC1, we used them engineer two novel Cre-driver lines, Xcr1Cre...
Abstract Despite being implicated in non-lymphoid tissues, non-recirculating T cells may also exist secondary lymphoid organs (SLO). However, a detailed characterization of this lymphoid-resident cell pool has not yet been done. Here we show that substantial proportion CD4 regulatory (Treg) and memory (Tmem) establish long-term residence the SLOs specific pathogen-free mice. Of these SLOs, only within Peyer’s patches is affected by microbiota. Resident Treg Tmem from lymph nodes tissues...
How intestinal epithelial cells interact with the microbiota and how this is regulated at gene expression level are critical questions. Smarcad1 a conserved chromatin remodeling factor poorly understood tissue function. As highly expressed in stem proliferative zones of epithelium, we explore its role tissue.Specific deletion mouse epithelium leads to colitis resistance substantial changes expression, including striking increase several genes linked innate immunity. Absence accessibility...
Summary We previously found that uptake of cellular debris prompts conventional dendritic cells (cDCs) to undergo maturation. This transformation results in DCs entering the molecular state termed ‘mregDC’. In this state, mregDCs dampen their ability acquire new antigens, upregulate chemokine receptors migrate lymphoid organs, and MHC-I -II, co-stimulatory, -inhibitory molecules promote differentiation antigen-specific T cells. Here, we show cholesterol mobilization – through both de novo...
ABSTRACT Here, we leveraged a large neoadjuvant PD-1 blockade trial in patients with hepatocellular carcinoma (HCC) to search for correlates of response immune checkpoint (ICB) within T cell-rich tumors. We show that ICB correlated the clonal expansion intratumoral CXCL13 + CH25H IL-21 CD4 helper cells (CXCL13 Th) and Granzyme K effector-like CD8 cells, whereas terminally exhausted CD39 hi TOX dominated non-responders. Strikingly, most cell receptor (TCR) clones expanded post-treatment were...
Monocyte-derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis bone marrow (BM) fuels these populations. Here, we performed paired transcriptome chromatin analysis over continuum of BM myeloid progenitors, circulating monocytes, tumor-infiltrating mo-macs mice patients with lung cancer to identify progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing accessibility histone mark changes, show tumors prime for Nfe2l2...
Visium is a spatial sequencing technology that utilizes messenger RNA (mRNA) to spatially map gene expression within tissues. Despite its potential, research utilizing deconvolution tools and exploring microenvironment dynamics remains challenging. We address this gap by benchmarking across diverse biological contexts, identifying optimal methodologies. Subsequently, we introduce novel pipeline integrating advanced techniques for reproducible tissue analysis. Through approach, uncover...
<h3>Background</h3> Most cancers are diseases of aging. But the lack an unbiased inquiry into cellular basis for link between aging and tumorigenesis has left study cancer incomplete. Filling this gap in knowledge could help characterize early stages aid design prevention strategies. Non-small cell lung (NSCLC) is strongly associated with As it most common cause cancer-related mortality, we sought to decipher effect on host response NSCLC pathogenesis. <h3>Methods</h3> We combined...
Abstract Our prior research established that the uptake of tumor debris induces maturation in conventional dendritic cells (cDCs), transforming them into a molecular state termed mature DCs enriched immunoregulatory molecules 'mregDC.' This entails dampened ability to acquire new antigens, upregulated chemokine receptors for migration lymphoid organs, and increased expression MHC-I -II, costimulatory, -inhibitory molecules, promoting differentiation antigen-specific T cells. Understanding...
<h3>Background</h3> Our prior research established that the uptake of tumor debris induces maturation in conventional dendritic cells (cDCs), transforming them into a molecular state termed 'mregDC.' This entails dampened ability to acquire new antigens, upregulated chemokine receptors for migration lymphoid organs, and increased expression MHC-I -II, co-stimulatory, -inhibitory molecules, promoting differentiation antigen-specific T cells.<sup>1</sup> Understanding dynamics accompanying...
Abstract Tertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS associated with better prognosis and enhanced response to immunotherapy, making these attractive therapeutic targets. However, the mechanisms regulating formation maintenance cancer incompletely understood. Using spatial transcriptomics multiplex imaging across various human tumors, we found an enrichment of mature dendritic cells (DC) expressing high...
The persistence of adoptively transferred T cells is vital for anti-tumor efficacy. Chimeric antigen receptor (CAR) can persist indefinitely when delivered to patients with B cell cancers and confer long-term remission. For solid tumors, however, sustaining CAR activity remains a major challenge. This has been attributed in part the immune microenvironment within though contribution specific subsets resistance not clear. Here we resolve how immunology irradiated tumors dramatically enhances...
Abstract Type-2 cytokines are hypothesized to promote an immune-permissive milieu for cancer grow. Through scRNAseq and CITEseq on human non-small cell lung (NSCLC) the krasG12Dp53−/− model we previously described a tumor-enriched dendritic program of concomitant immunosuppression activation which termed “mregDC,” that was also notable strong Th2 immune signature. We subsequently blocked canonical cytokine IL-4 in vivo tumor-bearing mice, found this significantly decreased tumor burden,...