A5001841343- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Cardiac electrophysiology and arrhythmias
- RNA Interference and Gene Delivery
- Gastrointestinal motility and disorders
- Chronic Myeloid Leukemia Treatments
- Receptor Mechanisms and Signaling
- Chronic Lymphocytic Leukemia Research
- Heart Rate Variability and Autonomic Control
- Glycosylation and Glycoproteins Research
- Cytomegalovirus and herpesvirus research
- Ion channel regulation and function
- Virus-based gene therapy research
- Hematopoietic Stem Cell Transplantation
- Biosimilars and Bioanalytical Methods
- Lymphoma Diagnosis and Treatment
- Nitric Oxide and Endothelin Effects
- Dermatology and Skin Diseases
- Hormonal Regulation and Hypertension
- Neuroscience of respiration and sleep
University of Lausanne
2013-2024
Ludwig Cancer Research
2015-2024
Porsolt (France)
2009-2024
Université Paris 8
2022-2024
University Hospital of Lausanne
2001-2023
Swiss Cancer Center Léman
2023
Centre Hospitalier De Pau
2023
Université Savoie Mont Blanc
2022
Université Lumière Lyon 2
2022
Vincennes University
2022
The paradoxical coexistence of spontaneous tumor antigen–specific immune responses with progressive disease in cancer patients furthers the need to dissect molecular pathways involved tumor-induced T cell dysfunction. In advanced melanoma, we have previously shown that cancer-germline antigen NY-ESO-1 stimulates NY-ESO-1–specific CD8+ cells up-regulate PD-1 expression. We also observed regulates expansion upon chronic stimulation. present study, show a fraction PD-1+ melanoma up-regulates...
Abstract Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result tumor eradication. We aimed at studying directly the functional efficacy of T cells site immune attack. Tumor lesions lymphoid and nonlymphoid tissues (metastatic lymph nodes soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients investigated for presence function specific differentiation antigen Melan-A/MART-1. Comparative analysis was...
Cytotoxic T cells that are present in tumors and capable of recognizing tumor epitopes nevertheless generally impotent eliciting rejection. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T-cell dysfunction may reveal effective strategies therapy. The inhibitory receptors PD-1 Tim-3 known to negatively regulate responses directed against well-characterized antigen NY-ESO-1. Here, we report upregulation molecule BTLA also plays a critical role...
The precise identification of Human Leukocyte Antigen class I (HLA-I) binding motifs plays a central role in our ability to understand and predict (neo-)antigen presentation infectious diseases cancer. Here, by exploiting co-occurrence HLA-I alleles across ten newly generated as well forty public HLA peptidomics datasets comprising more than 115,000 unique peptides, we show that can rapidly accurately identify many map them their corresponding without any priori knowledge specificity. Our...
Fully functional, tumor-specific, SLAMF7-expressing cytotoxic CD4 T cells directly mediate immunity against human cancer.
The recognition of pathogen or cancer-specific epitopes by CD8+ T cells is crucial for the clearance infections and response to cancer immunotherapy. This process requires be presented on class I human leukocyte antigen (HLA-I) molecules recognized T-cell receptor (TCR). Machine learning models capturing these two aspects immune are key improve epitope predictions. Here, we assembled a high-quality dataset naturally HLA-I ligands experimentally verified neo-epitopes. We then integrated data...
CD4+ T cells orchestrate the adaptive immune response against pathogens and cancer by recognizing epitopes presented on class II major histocompatibility complex (MHC-II) molecules. The high polymorphism of MHC-II genes represents an important hurdle toward accurate prediction identification cell epitopes. Here we collected curated a dataset 627,013 unique ligands identified mass spectrometry. This enabled us to precisely determine binding motifs 88 alleles across humans, mice, cattle,...
The success of cancer immunotherapy depends in part on the strength antigen recognition by T cells. Here, we characterize cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities 371 CD8 clones specific for neoantigens, tumor-associated antigens (TAAs) or viral isolated from tumors blood patients healthy donors. cells exhibit stronger avidity than their counterparts. Relative to TAA, neoantigen-specific are higher and, consistently,...
Although melanoma vaccines stimulate tumor antigen-specific CD8(+) T cells, objective clinical responses are rarely observed. To investigate this discrepancy, we evaluated the character of vaccine-induced cells with regard to inhibitory T-cell coreceptors PD-1 and Tim-3 in patients metastatic who were administered vaccines. The included incomplete Freund's adjuvant, CpG oligodeoxynucleotide (CpG), HLA-A2-restricted analog peptide NY-ESO-1 157-165V, either by itself or combination pan-DR...
The programmed death 1 (PD-1) receptor is a negative regulator of activated T cells and up-regulated on exhausted virus-specific CD8(+) in chronically infected mice humans. Programmed ligand (PD-L1) expressed by multiple tumors, its interaction with PD-1 resulted tumor escape experimental models. To investigate the role impairing spontaneous Ag-specific melanoma patients, we have examined effect expression ex vivo detectable specific to Ag NY-ESO-1. In contrast EBV, influenza, or...
HLA-I molecules bind short peptides and present them for recognition by CD8+ T cells. The length of ligands typically ranges from 8 to 12 aa, but variability is observed across different alleles. In this study we collected recent in-depth HLA peptidomics data, including newly generated peptidomes (31,896 unique peptides) human meningioma samples, analyze the peptide distribution multiple specificity 84 We a clear clustering alleles with distinct distributions, which enabled us structural...
Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load types remains unknown. Comprehensive and deep analysis circulating tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8
Through a rational design approach, we generated panel of HLA-A*0201/NY-ESO-1(157-165)-specific T cell receptors (TCR) with increasing affinities up to 150-fold from the wild-type TCR. Using these TCR variants which extend just beyond natural affinity range, along an extreme supraphysiologic one having 1400-fold enhanced affinity, and low-binding one, sought determine effect binding properties cognate peptide concentration on CD8(+) responsiveness. Major histocompatibility complexes (MHC)...
The identification of patient-specific tumor antigens is complicated by the low frequency T cells specific for each antigen. Here we describe NeoScreen, a method that enables sensitive rare (neo)antigens and cognate cell receptors (TCRs) expressed tumor-infiltrating lymphocytes. transduced with antigen-specific TCRs identified NeoScreen mediate regression established tumors in patient-derived xenograft mice.
T cell receptor (TCR) technologies, including repertoire analyses and engineering, are increasingly important in the clinical management of cellular immunity cancer, transplantation, other immune diseases. However, sensitive reliable methods for TCR cloning still lacking. Here, we report on SEQTR, a high-throughput approach to analyze human mouse repertoires that is more sensitive, reproducible, accurate as compared with commonly used assays, thus reliably captures complexity blood tumor...
The low frequency of self-peptide–specific T cells in the human preimmune repertoire has so far precluded their direct evaluation. Here, we report an unexpected high specific for self-antigen Melan-A/MART-1 CD8 single–positive thymocytes from histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained peripheral blood newborns and adults. Postthymic replicative history Melan-A/MART-1–specific was independently assessed by quantifying cell receptor excision circles...
Abstract Although increasing evidence suggests that CTL are important to fight the development of some cancers, frequency detectable tumor-specific T cells is low in cancer patients, and these have generally poor functional capacities, compared with virus-specific CD8+ cells. The generation a vaccine potent responses against tumor Ags therefore remains major challenge. In present study, ex vivo analyses Melan-A-specific following vaccination Melan-A peptide CpG oligodeoxynucleotides revealed...
Abstract The identification of CTL-defined tumor-associated Ags has allowed the development new strategies for cancer immunotherapy. To potentiate CTL responses, peptide-based vaccines require coadministration adjuvants. Because oligodeoxynucleotides (ODN) containing CpG motifs are strong immunostimulators, we analyzed ability ODN to act as adjuvant response against tumor-derived synthetic peptide in absence or presence IFA. Mice transgenic a chimeric MHC class I molecule were immunized with...
The present study evaluates the potential of third-generation lentivirus vectors with respect to their use as in vivo–administered T cell vaccines. We demonstrate that lentivector injection into footpad mice transduces DCs appear draining lymph node and spleen. In addition, a vaccine bearing antigen induced very strong systemic antigen-specific cytotoxic lymphocyte (CTL) responses mice. Comparative vaccination performed two different models demonstrated vivo administration was superior...