A5031142553- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- T-cell and B-cell Immunology
- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Immune Cell Function and Interaction
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Tryptophan and brain disorders
- Viral-associated cancers and disorders
- Trace Elements in Health
- Glycosylation and Glycoproteins Research
- HIV Research and Treatment
- Ubiquitin and proteasome pathways
- Pancreatic and Hepatic Oncology Research
- Antimicrobial Peptides and Activities
- Circular RNAs in diseases
- Advanced biosensing and bioanalysis techniques
- Multiple Myeloma Research and Treatments
- Metabolomics and Mass Spectrometry Studies
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
Ludwig Cancer Research
2018-2025
University of Lausanne
2018-2025
University Hospital of Lausanne
2018-2024
Swiss Cancer Center Léman
2020-2024
Ludwig Cancer Research
2024
Agora
2024
Cancer Research Center
2020
Abstract Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA derived from annotated non-coding regions could elicit anti-tumor immune responses. However, sensitive and accurate mass spectrometry (MS)-based proteogenomics approaches are required robustly these peptides. We present an MS-based analytical approach characterizes...
Activated T cells secrete interferon-γ, which triggers intracellular tryptophan shortage by upregulating the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme1-4. Here we show that despite depletion, in-frame protein synthesis continues across codons. We identified tryptophan-to-phenylalanine codon reassignment (W>F) as major event facilitating this process, and pinpointed tryptophanyl-tRNA synthetase (WARS1) its source. call these W>F peptides 'substitutants' to distinguish them from genetically...
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,...
Abstract One key barrier to improving efficacy of personalized cancer immunotherapies that are dependent on the tumor antigenic landscape remains patient stratification. Although patients with CD3 + CD8 T cell-inflamed tumors typically show better response immune checkpoint inhibitors, it is still unknown whether immunopeptidome repertoire presented in highly inflamed and noninflamed substantially different. We surveyed 61 regions adjacent nonmalignant lung tissues from 8 performed deep...
Circular RNAs (circRNAs) are covalently closed non-coding lacking the 5' cap and poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed in human cancers could be an unexplored source of tumor-specific antigens, potentially mediating anti-tumor T cell responses. This study presents immunopeptidomics workflow with a specific focus on generating circRNA-specific protein fasta reference. The main goal this is to...
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...
<h3>Background</h3> Patient derived organoids (PDOs) can be established from colorectal cancers (CRCs) as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics investigate neoantigen presentation whether this augmented through interferon gamma (IFNγ) or MEK-inhibitor treatment. <h3>Methods</h3> Four microsatellite stable PDOs chemotherapy refractory one a treatment naïve CRC were expanded replicates with 100 million...
Mass spectrometry (MS) is the state-of-the-art methodology for capturing breadth and depth of immunopeptidome across human leukocyte antigen (HLA) allotypes cell types. The majority studies in immunopeptidomics field are discovery driven. Hence, data-dependent tandem MS (MS/MS) acquisition (DDA) widely used, as it generates high-quality references peptide fingerprints. However, DDA suffers from stochastic selection abundant ions that impairs sensitivity reproducibility. In contrast,...
The accurate selection of neoantigens that bind to class I human leukocyte antigen (HLA) and are recognized by autologous T cells is a crucial step in many cancer immunotherapy pipelines. We reprocessed whole-exome sequencing RNA (RNA-seq) data from 120 patients two external large-scale neoantigen immunogenicity screening assays combined with an in-house dataset 11 identified 46,017 somatic single-nucleotide variant mutations 1,781,445 neo-peptides, which 212 178 neo-peptides were...
Decreased antigen presentation contributes to the ability of cancer cells evade immune system. We used minimal gene regulatory network type 1 conventional dendritic (cDC1) reprogram into professional antigen-presenting (tumor-APCs). Enforced expression transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient induce cDC1 phenotype in 36 cell lines derived from human mouse hematological solid tumors. Within 9 days reprogramming, tumor-APCs acquired transcriptional epigenetic programs...
Neoepitopes are the only truly tumor-specific antigens. Although potential neoepitopes can be readily identified using genomics, that mediate tumor rejection constitute a small minority, and there is little consensus on how to identify them. Here, for first time, we use combination of unbiased discovery MS immunopeptidomics targeted directly elicit actual in mice. We report MS-identified an astonishingly rich source mediating neoepitopes. has also demonstrated unambiguously presentation by...
Despite the promising therapeutic effects of immune checkpoint blockade (ICB), most patients with solid tumors treated anti-PD-1/PD-L1 monotherapy do not achieve objective responses, tumor regressions being partial rather than complete. It is hypothesized that absence pre-existing antitumor immunity and/or presence additional suppressive factors at microenvironment are responsible for such failures. therefore clear in order to fully exploit potential PD-1 therapy, response should be...
The presentation of peptides on class I human leukocyte antigen (HLA-I) molecules plays a central role in immune recognition infected or malignant cells. In cancer, non-self HLA-I ligands can arise from many different alterations, including non-synonymous mutations, gene fusion, cancer-specific alternative mRNA splicing aberrant post-translational modifications. Identifying remains challenging task that requires either heavy experimental work for vivo identification optimized bioinformatics...
Mass spectrometry (MS)-based immunopeptidomics is an attractive antigen discovery method with growing clinical implications. However, the current experimental approach to extract HLA-restricted peptides requires a bulky sample source, which remains challenge for obtaining specimens. We present innovative workflow that low volume, streamlines immunoaffinity purification (IP) and C18 peptide cleanup on single microfluidics platform automated liquid handling minimal transfers, resulting in...
The accurate identification and prioritization of antigenic peptides is crucial for the development personalized cancer immunotherapies. Publicly available pipelines to predict clinical neoantigens do not allow direct integration mass spectrometry immunopeptidomics data, which can uncover derived from various canonical noncanonical sources. To address this, we present an end-to-end proteogenomic pipeline, called NeoDisc, that combines state-of-the-art publicly in-house software...
Abstract Heterochromatin loss and genetic instability enhance cancer progression by favoring clonal diversity, yet uncontrolled replicative stress leads to mitotic catastrophe inflammatory responses that promote immune rejection. KRAB domain-containing zinc finger proteins (KZFP) contribute heterochromatin maintenance at transposable elements (TE). Here, we identified an association of upregulation a cluster primate-specific KZFPs with poor prognosis, increased copy-number alterations,...
Harnessing the immune system to purposely recognize and destroy tumors represents a significant breakthrough in clinical oncology. Non-synonymous mutations (neoantigenic peptides) were identified as powerful cancer targets. This knowledge can be exploited for further improvements of active immunotherapies, including vaccines, T cells specific neoantigens are not attenuated by tolerance mechanism do harm healthy tissues. The current study aimed at developing an optimized multitarget vaccine...
Current HIV vaccines designed to stimulate CD8+ T cells have failed induce immunologic control upon infection. The functions of vaccine-induced HIV-specific were investigated here in detail. Cytotoxic capacity was significantly lower than controllers and not a consequence low frequency or unaccumulated functional cytotoxic proteins. Low attributable impaired degranulation response the antigen levels present on HIV-infected targets. cell receptor (TCR) repertoire polyclonal transduction these...
CD4+ T cell responses are crucial for inducing and maintaining effective anticancer immunity, the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to development potent cancer immunotherapies. In many tumor types, especially in glioblastoma (GBM), HLA-II complexes hardly ever naturally expressed. Hence, little known about immunogenic GBM. With stable expression major histocompatibility complex transactivator (CIITA) coupled a detailed sensitive mass...
High-affinity MHC I-peptide interactions are considered essential for immunogenicity. However, some neo-epitopes with low affinity I have been reported to elicit CD8 T cell dependent tumor rejection in immunization-challenge studies. Here we show a mouse model that neo-epitope poorly binds is able enhance the immunogenicity of absence immunization. Fibrosarcoma cells naturally occurring mutation edited their wild type counterpart; then re-introduced order obtain line genetically identical...
The human leukocyte antigen (HLA) processing and presentation machinery (APPM) is altered in various diseases response to drug treatments. Defects the may change levels or alter repertoire of presented peptides, globally an HLA allele restricted manner, with direct implications for adaptive immunity. In this study, we investigated immunopeptidome landscape across a panel isogenic HAP1 cell line clones each knock-out single gene encoding key protein APPM, including B2M, TAP1, TAP2, TAPBP,...
Background Novel therapeutic strategies in ovarian cancer (OC) are needed as the survival rate remains dismally low. Although dendritic cell-based vaccines effective eliciting responses, their complex and costly manufacturing process hampers full clinical utility outside specialized clinics. Here, we describe a novel approach of generating rapid vaccine using ascites-derived monocytes for treating OC. Methods Using ID8 mouse tumor model OC patient samples, isolated ascites evaluated them...