Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neoantigen Discovery and Validation in Hepatocellular Carcinoma: Unveiling Immunogenic Targets Through Mass Spectrometry

ABSTRACT: The accurate identification of tumor neoantigens, particularly cryptic antigens from non-canonical translation, is crucial for developing effective cancer immunotherapies. However, the significance and action of cryptic antigens in anti-tumour immunity remain unclear. In this study, we utilized a highly sensitive mass spectrometry-based de novo sequencing approach to identify non-canonical MHC-binding immunopeptides and evaluate the anti-tumor immune effects of vaccines composed of these peptides in Hepatocellular carcinoma (HCC).

ORGANISM(S): Rattus Rattus

SUBMITTER: Xiaolong Liu

PROVIDER: PXD079354 | iProX | Fri Jul 25 00:00:00 BST 2025

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

Mass spectrometry-based de novo sequencing reveals non-canonical neoantigens with antitumor efficacy in hepatocellular carcinoma.

Xing Xiaohua X Liu Mingxin M Ouyang Jiahe J Tang Yaxin Y Shan Baozhen B Tang Ruijing R Hu En E Li Ming M Liu Xiaolong X

JHEP reports : innovation in hepatology 20260213 4

<h4>Background & aims</h4>Tumor neoantigens, especially cryptic antigens from non-canonical translation, are vital for cancer immunotherapy. Mass spectrometry (MS)-based de novo sequencing identifies candidates, but unverified immunogenicity and antitumor efficacy limit clinical applicability. This study aimed to identify novel non-canonical neoantigens in hepatocellular carcinoma (HCC) using MS-based de novo sequencing and rigorously validate their immunogenicity and antitumor efficacy.<h4>Meth ...[more]

PMID: 41861674

Similar Datasets

Mapping of immunopeptidome of cancer immunotherapy with oncolytic virus and checkpoint blockade

Project description:The elucidation of therapy-induced changes to the class I major histocompatibility complex (MHC-I)-bound tumor antigens is crucial for understanding immune-mediated tumor eradication and identifying potential targets for peptide vaccines to enhance the efficacy of immunotherapies. Here, we investigated how oncolytic reovirus therapy with and without immune checkpoint blockade (ICB) alters the tumor peptide-MHC repertoire. Using mass spectrometry analysis of immunoaffinity purified MHC peptides, we first showed that changes to the MHC immunopeptidome following reovirus treatment is cancer type-dependent, where a murine fibrosarcoma model displayed quantitative and qualitative variance in differentially expressed peptides (DEPs) as compared to those identified in a murine ovarian cancer model. We then determined that the combination therapy of reovirus and ICB in the fibrosarcoma model resulted in higher numbers of DEPs relative to either monotherapy alone. Most importantly, we identified reovirus and ICB-induced MHC peptides that are biologically active in stimulating interferon-gamma response in cognate CD8+ T cells, which likely contribute to cancer immunoediting. These findings highlight the importance of therapy-induced changes to the MHC immunopeptidome in shaping the underlying anti-tumor immune responses during reovirus and ICB combination therapy.

2021-12-06 | PXD024369 | Pride

LC-MSMS of primary AML class I immunopeptidome (Canonical personalized proteome)

Project description:The development of therapeutic anticancer vaccines calls for the identification of tumor-specific antigens (TSAs). Though a combination of four cutting-edge proteogenomic approaches, we performed a deep exploration of the MHC-I presented peptides (MAPs) of 19 acute myeloid leukemia (AML) patients and identified various TSAs that could serve for the design of an anti-AML vaccine.

2021-03-19 | PXD018541 | Pride

LC-MSMS of primary AML class I immunopeptidome (mTECs+MPCs k-mer depletion approach)

2021-03-19 | PXD018539 | Pride

LC-MSMS of primary AML class I immunopeptidome (mTECs k-mer depletion approach)

2021-03-19 | PXD018540 | Pride

LC-MSMS of primary AML class I immunopeptidome (ERE-derived MAPs identification approach)

2021-03-19 | PXD018542 | Pride

LC-MSMS of primary AML class I immunopeptidome (differential k-mer expression approach)

2021-03-19 | PXD018543 | Pride

Checkpoint Blockade Cancer Immunotherapy Targets Tumor-Specific Mutant Antigens

Project description:Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and Programmed death-1 (PD-1) are immunoregulatory receptors expressed on T cells that play important roles in suppressing immune responses to cancer. Although monoclonal antibodies that target CTLA-4 or PD-1 stimulate therapeutic anti-tumour T cell responses, the tumour antigens recognized by checkpoint blockade immunotherapy remain undefined. Herein, we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T cell rejection antigens following αPD-1 and/or αCTLA-4 treatment of mice bearing progressively growing sarcomas. We validate this conclusion by showing that (a) the predicted mutant epitopes associate with MHC class I molecules of the tumour; (b) T cells specific for these mutant epitopes infiltrate tumours; and (c) therapeutic vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Whereas, T cells with the same antigen specificity are present in progressively growing tumours in control mice, tumour-specific T cells in αPD-1- and/or αCTLA-4-treated mice express some overlapping but mostly treatment-specific transcriptional profiles that render them capable of tumour rejection. Thus, tumour-specific mutant antigens are not only important targets of checkpoint blockade therapy but also can be used to identify tumour antigen-specific T cells that function as biomarkers of successful anti-tumour responses.

2014-11-07 | GSE62771 | GEO

Personalized Neoantigen Cancer Vaccine in Glioblastoma Multiforme

Project description:<p>Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection. We demonstrated that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load and an immunologically ‘cold’ tumour microenvironment. Here we conducted whole-exome sequencing of tumor and normal cells from individual patients with glioblastoma to identify tumor-specific mutations. We assessed the expression of mutated alleles by RNA-sequencing of tumor. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone-a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma.</p>

| phs001519 | dbGaP

LC-MSMS of primary breast cancer samples

Project description:CD8 T cells drive the anti-cancer immune response through the recognition of MHC I-associated peptides. In order to identify relevant targets for cancer immunotherapy in breast cancer, we characterized the immunopeptidome of 26 primary breast cancer samples from two different subtypes, hormone-receptor positive (n=14) and triple negative (n=12). We were able to identify tumor-specific and tumor associated antigens in both subtypes of breast cancer, which can be used for the development of anti-cancer vaccines or as targets for engineered T-cells.

2023-11-15 | PXD034818 | Pride

Identification of antigens presented by MHC for vaccines against tuberculosis

Project description:The immune response against tuberculosis relies, at least in part, on CD4+ T cells. Protective vaccines require the induction of antigen-specific CD4+ T cells via mycobacterial peptides presented by MHC class-II in infected macrophages. We have purified MHC class-I and MHC-II peptides and analysed them by mass spectrometry. We have successfully identified 97 mycobacterial peptides presented by MHC-II and 54 presented by MHC-I, from 76 and 41 antigens, respectively. The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cells from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease. Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model. When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying novel candidate antigens.

2020-01-08 | E-MTAB-8057 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data