A5066269629- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Advanced Proteomics Techniques and Applications
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Mass Spectrometry Techniques and Applications
- Viral-associated cancers and disorders
- Trace Elements in Health
- Esophageal Cancer Research and Treatment
- Glycosylation and Glycoproteins Research
- HIV Research and Treatment
- Cancer Immunotherapy and Biomarkers
- Antimicrobial Peptides and Activities
- Metabolomics and Mass Spectrometry Studies
- Immune cells in cancer
- CAR-T cell therapy research
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
- Analytical Chemistry and Chromatography
- RNA Interference and Gene Delivery
Ludwig Cancer Research
2017-2025
University of Lausanne
2017-2025
University Hospital of Lausanne
2017-2024
University of Geneva
2013-2017
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...
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...
Comprehensive knowledge of the human leukocyte antigen (HLA) class-I and class-II peptides presented to T-cells is crucial for designing innovative therapeutics against cancer other diseases. However methodologies their purification mass-spectrometry analysis have been a major limitation. We designed novel high-throughput, reproducible sensitive method sequential immuno-affinity HLA-I -II from up 96 samples in plate format, suitable both cell lines tissues. Our methodology drastically...
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...
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,...
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...
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...
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,...
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...
Abstract 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...
Esophageal cancer is the eighth most common worldwide and majority of patients have systemic disease at presentation. adenocarcinoma (OAC), predominant subtype in western countries, largely resistant to current chemotherapy regimens. Selective markers are needed enhance clinical staging allow targeted therapies yet there minimal proteomic data on this type. After histological review, lysates from OAC matched normal esophageal gastric samples seven were subjected LC MS/MS after tandem mass...
Induction of an effective tumor immunity is a complex process that includes the appropriate presentation antigens, activation specific T cells, and elimination malignant cells. Potent efficient cell dependent on multiple factors, such as timely expression co-stimulatory molecules, differentiation state professional antigen presenting cells (e.g. dendritic cells; DCs), functionality processing machinery (APPM), repertoire HLA class I II-bound peptides (termed immunopeptidome) presented to So...
Hypochlorous acid (HOCl)-treated whole tumor cell lysates (Ox-L) have been shown to be more immunogenic when used as an antigen source for therapeutic dendritic (DC)-based vaccines, improving downstream immune responses both in vitro and vivo. However, the mechanisms behind improved immunogenicity are still elusive. To address this question, we conducted a proteomic immunopeptidomics analyses map modifications alterations introduced by HOCl treatment using human melanoma line model system....
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 derive 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 the...
Abstract Spliced peptides are short protein fragments spliced together in the proteasome by peptide bond formation. True estimation of contribution proteasome-spliced (PSPs) to global Human Leukocyte Antigen (HLA) ligandome is critical. A recent study suggested that PSPs contribute up 30% HLA ligandome. We performed a thorough reanalysis reported results using multiple computational tools and various validation steps concluded only fraction proposed passes quality filters. To better estimate...
Abstract 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 amino acids, but variability is observed across different alleles. Here 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 study...
Label free quantification using liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is widely used in quantitative proteomics. However, data-dependent bottom-up proteomics suffers from low reproducibility due to semi-random selection of precursor ions for spectrometry. In addition, this acquisition mode biased towards abundant peptides. To overcome these problems, alternative precursor-ion methods were developed, such as data-independent pseudo -multiple...