A5054642893- Melanoma and MAPK Pathways
- Mechanisms of cancer metastasis
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Chronic Myeloid Leukemia Treatments
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Adenosine and Purinergic Signaling
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Fibroblast Growth Factor Research
- Nuclear Receptors and Signaling
- Monoclonal and Polyclonal Antibodies Research
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- Cancer Mechanisms and Therapy
- Inflammatory Bowel Disease
University Hospital of Basel
2022-2025
University of Basel
2022-2025
MR1T cells are a recently found class of T that recognize antigens presented by the major histocompatibility complex-I–related molecule MR1 in absence microbial infection. The nature self-antigens stimulate remains unclear, hampering our understanding their physiological role and therapeutic potential. By combining genetic, pharmacological, biochemical approaches, we carbonyl stress changes nucleobase metabolism target promote cell activation. Stimulatory compounds formed adducts nucleobases...
Mucosal-associated invariant T (MAIT) cells use canonical semi-invariant cell receptors (TCR) to recognize microbial riboflavin precursors displayed by the antigen-presenting molecule MR1. The extent of MAIT TCR crossreactivity toward physiological, microbially unrelated antigens remains underexplored. We describe TCRs endowed with MR1-dependent reactivity tumor and healthy in absence metabolites. bearing crossreactive self are rare but commonly found within donors display T-helper-like...
The TCR-mediated activation of T cells expressing the TCR Vγ9Vδ2 relies on an innate-like mechanism involving butyrophilin 3A1, 3A2 and 2A1 molecules phospho-antigens, without participation classical antigen-presenting molecules. Whether also recognize complexes composed antigens in adaptive-like manner is unknown. Here, we identify MR1-autoreactive Vγ9Vδ2. This MR1-restricted response antigen- CDR3δ-dependent butyrophilin-independent. gene transfer reconstitutes MR1-antigen recognition,...
A significant challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive microenvironment, which densely populated by protumoral glioma-associated microglia and macrophages (GAMs). Myeloid immune checkpoint targeting the CD47-signal regulatory protein alpha (SIRPα) axis induces GAM phagocytic function, but CD47 blockade monotherapy associated with toxicity low bioavailability in solid tumors. In this work, we engineer a CAR epidermal...
Summary MR1T lymphocytes are a recently identified population of T cells that recognize unknown self-antigens presented by the non-polymorphic MHC-I-related molecule, MR1. can kill tumor and modulate functions other immune with promising therapeutic applications. By integrating genetic, pharmacological biochemical approaches we carbonyl stress alterations nucleobase metabolism in target promote recognition MR1 cells. We dissected these pathways found adduct-containing metabolites stimulating...
Abstract The MHC class I–related molecule MR1 is ubiquitously expressed, highly conserved among mammals, and presents bacterial endogenous antigens in tumor cells. These features indicate that tumor-specific T cells restricted to may represent ideal candidates for novel cancer-directed T-cell immunotherapy. very low expression of the protein at cell surface a potential challenge limiting possible use MR1-directed immunotherapies. To overcome this challenge, it important understanding...
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<p>Phenotype and TCR gene expression by MR1T cell clones</p>
<p>Supplementary Figure S1</p>
<p>List of genes regulated by BRAF inhibition</p>
<div>Abstract<p>The MHC class I–related molecule MR1 is ubiquitously expressed, highly conserved among mammals, and presents bacterial endogenous antigens in tumor cells. These features indicate that tumor-specific T cells restricted to may represent ideal candidates for novel cancer-directed T-cell immunotherapy. The very low expression of the protein at cell surface a potential challenge limiting possible use MR1-directed immunotherapies. To overcome this challenge, it...
Abstract Crohn’s disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. Extensive screening studies have revealed accumulation immune cell subsets with unique plasticity and immunoregulatory properties in patients CD. We performed phenotypic functional on inflamed non-inflamed bioptic tissue to investigate presence distinct T cells intestinal mucosa CD patients. analysed hundreds surface molecules expressed isolated from using anti-CD45 mAbs-based barcoding. A gene...
Abstract A major challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive tumor microenvironment (TME), which densely populated and supported by protumoral glioma-associated microglia macrophages (GAMs). Targeting of CD47, a “don’t-eat-me” signal overexpressed cells, disrupts the CD47-SIRPα axis induces GAM phagocytic function. However, antibody-mediated CD47 blockade monotherapy associated with toxicity low bioavailability in solid...