S2, S3 and S5 - HLA peptides plasma cancer
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ-Orbitrap
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: 
Arie Admon
LAB HEAD: Arie Admon
PROVIDER: PRD000180 | Pride | 2010-03-22
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| PRIDE_Exp_Complete_Ac_10648.pride.mgf.gz | Mgf | |||
| PRIDE_Exp_Complete_Ac_10648.pride.mztab.gz | Mztab | |||
| PRIDE_Exp_Complete_Ac_10648.xml.gz | Xml |
Items per page: 5 1 - 3 of 3 |
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Project description:Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Furthermore, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples and the membranal HLA of GBM tumors of 10 tumor samples of the same patients. Tumor samples were fresh-frozen immediately after surgery and plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the same patients; yet, low correlations were observed between these HLA peptidomes and the tumors’ proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.
2019-06-11 | PXD008127 | Pride
Project description:Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Furthermore, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples and the membranal HLA of GBM tumors of 10 tumor samples of the same patients. Tumor samples were fresh-frozen immediately after surgery and plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the same patients; yet, low correlations were observed between these HLA peptidomes and the tumors’ proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.
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Project description:Whether the presentation levels of the major histocompatibility complex (MHC, called the human leukocytes antigens, HLA, in humans) is limited by the availability of peptide ligands for loading or by the supply of empty MHC molecules, is a yet unresolved issue. This study aims to tackle this dilemma using large-scale immunopeptidome analyses. First, cultured cells (MCF-7) were treated with interferons, which dramatically increased presentation levels of their HLA-B molecules, much more than HLA-A and HLA-C. The differential increase in the HLA-B molecules with their bound peptides, was driven by elevated HLA synthesis levels and not by supply of peptides, since all three HLA allotypes draw peptides from the same peptide pool, which should have been affected similarly by the interferons treatment. In addition, artificial competition for peptides was created by recombinant high levels expression of soluble HLA-A*02:01 molecules, in the same MCF-7 cells and on top of their endogenous membranal HLA-A*02:01. This high level expression of the soluble HLA did not affect the endogenous membranal HLA-A*02:01 peptidomes or its cell surface presentation levels. We therefore concluded that a surplus supply of peptides is available for loading and that presentation levels are more likely limited by the supply of HLA molecules.
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Project description:Abstract Background and aims. Hepatocellular carcinoma (HCC) shows limited response to checkpoint inhibitors, leaving opportunity for antigen-based immunotherapy and improved disease monitoring. This study evaluates plasma-derived soluble HLA-I (sHLA-I) peptidome as a minimally invasive source of tumor antigens by comparing them to tumor and adjacent tissue HLA ligands to assess its value for personalized treatment and diagnostics in HCC. Methods. Plasma-derived soluble HLA-I complexes and membranous HLA-I ligands from paired tumor and adjacent liver tissues of HCC and non-HCC control patients were isolated using pan-HLA-I immunoprecipitation and analyzed by LC-MS/MS. Peptide identification and patient-specific HLA binding predictions were complemented by annotation of tumor-associated antigens (TAAs) to compare ligand repertoires across HLA sources. Results The plasma soluble HLA-I (sHLA-I) peptidome from HCC and non-HCC patients was successfully characterized, with 1,553 to 9,421 unique peptides identified per sample after contaminant filtering. Peptides were enriched for canonical 8–11-mer lengths, with most predicted to bind patient-specific HLA-I alleles. Among 3,907 source proteins delivering peptides to the HCC sHLA-I peptidome, 815 were unique to HCC patients, and protein interaction analysis revealed significantly increased network connectivity centered around tumor-associated proteins. Comparison with membranous HLA-I (mHLA-I) peptidomes from tumor and adjacent tissues yielded 20 peptides from 17 tumor-associated antigens (TAAs) that were shared between sHLA-I and mHLA-I. Nine of these were only identified from HCC plasma and not from non-HCC controls, five overlapped with tumor mHLA-I. Conclusions. This pilot study demonstrates that the plasma-derived soluble HLA-I immunopeptidome in HCC patients contains peptides derived from TAAs, at least partially reflective of those presented on tumor tissue. These findings support the potential of sHLA-I profiling as a minimally invasive strategy for identifying actionable targets and tumor-specific signatures in HCC. Future improvements in analytical sensitivity and throughput, and validation in larger cohorts are now needed to establish its clinical utility.
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Project description:Few non-classical HLA-E restricted HIV-specific epitopes have been described, and even less is known about the functional profile of responding CD8 T cells (CD8s). This study evaluates the functional characteristics of CD8s targeting the Gag epitope (KAFSPEVIPMF or KF11) based on their restriction by either HLA-E (E-CD8s) or HLA-B57 (B57-CD8s). CD8s from 8 people with HIV (PWH) were cocultured with KF11 peptide presented by cell lines expressing HLA-B*57:01, HLA-E*01:01 or E*01:03. CD8s were analyzed through single-cell (sc) RNA and TCR sequencing. Additionally, supernatants were analyzed for soluble proteomics using a Luminex assay. B57-CD8s secreted higher levels of cytotoxic cytokines such as IFNγ, while E-CD8s produced more chemotactic cytokines, including RANTES, CXCL10 (IP-10), and IL27confirmed through scRNAseq. Despite distinct cytokine profiles, TCR clonotypes stimulated by KF11 were cross-restricted by HLA-B*57 and HLA-E*01/03. In vitro T cell reporter assays clearly demonstrated this cross-restriction. A TRAV5-containing metaclonotype cluster was seen in PWH with lower viral loads. These findings demonstrate that HIV-specific CD8s in PWH exhibit cross HLA-B*57 and HLA-E*01/03 restriction, resulting in functionally distinct immune responses that may contribute to HIV control.
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