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Immunopeptidome of an acute myeloid leukemia cell line THP1

ABSTRACT: We report the use of complementary peptide antigen enrichment and comprehensive mass spectrometric acquisition strategies to provide in-depth immunopeptidome data for AML cell line THP1

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Anthony Wayne Purcell

PROVIDER: MSV000087786 | MassIVE | Fri Jul 09 07:39:00 BST 2021

SECONDARY ACCESSION(S): PXD015039

REPOSITORIES: MassIVE

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In-depth mining of the immunopeptidome of an acute myeloid leukemia cell line using complementary ligand enrichment and data acquisition strategies.

Pandey Kirti K Mifsud Nicole A NA Lim Kam Sian Terry C C TCC Ayala Rochelle R Ternette Nicola N Ramarathinam Sri H SH Purcell Anthony W AW

Molecular immunology 20200505

The identification of T cell epitopes derived from tumour specific antigens remains a significant challenge for the development of peptide-based vaccines and immunotherapies. The use of mass spectrometry-based approaches (immunopeptidomics) can provide powerful new avenues for the identification of such epitopes. In this study we report the use of complementary peptide antigen enrichment methods and a comprehensive mass spectrometric acquisition strategy to provide in-depth immunopeptidome data ...[more]

PMID: 32387766

Similar Datasets

Immunopeptidome of an acute myeloid leukemia cell line THP1

Project description:We report the use of complementary peptide antigen enrichment and comprehensive mass spectrometric acquisition strategies to provide in-depth immunopeptidome data for AML cell line THP1

2020-05-13 | PXD015039 | Pride

Immune surveillance of acute myeloid leukemia is mediated by HLA-presented antigens on leukemia progenitor cells

Project description:Persistent therapy-resistant leukemic progenitor cells (LPC) are a main cause of disease relapse and recurrence in acute myeloid leukemia (AML). Specific LPC-targeting therapies may thus improve treatment outcome of AML patients. We demonstrate that LPCs present human leukocyte antigen (HLA)-restricted cancer antigens that induce T cell responses allowing for immune surveillance of AML. Using a mass spectrometry-based immunopeptidomics approach we characterized the antigenic landscape of patient LPCs and identify AML/LPC-associated HLA-presented antigens as well as mutation-derived and cryptic neoepitopes as prime targets for development of T cell-based immunotherapeutic approaches. We observed frequent spontaneous memory T cells targeting these AML/LPC-associated antigens in AML patients and showed that antigen-specific T cell recognition and HLA class II immunopeptidome diversity impacts clinical outcome. Our results pave the way for implementation of AML/LPC-associated antigens for T cell-based immunotherapeutic approaches to specifically target and eliminate residual LPCs in AML patients.

2023-08-23 | PXD038691 | Pride

Discovery of tumor specific antigens in acute myeloid leukemia.

Project description:We performed RNA-Seq and mass spectrometry (MS) on the immunopeptidome of 19 human primary AML samples and discovered a set of 58 tumor specific antigens (TSA) that could serve to design an anti-AML immunotherapy.

2021-03-15 | GSE147524 | GEO

Immune surveillance of acute myeloid leukemia is mediated by HLA-presented antigens on leukemia progenitor cells

Project description:Persistent therapy-resistant leukemia progenitor cells (LPC) are a main cause of disease relapse and recurrence in acute myeloid leukemia (AML). Specific LPC-targeting therapies may thus improve treatment outcome of AML patients. We demonstrated that LPCs present human leukocyte antigen (HLA)-restricted cancer antigens that induce T cell responses allowing for immune surveillance of AML. Using a mass spectrometry-based immunopeptidomics approach, we characterized the antigenic landscape of patient LPCs and identified AML/LPC-associated HLA-presented antigens including mutation-derived and cryptic neoepitopes as prime targets for development of T cell-based immunotherapeutic approaches. We observed frequent spontaneous memory T cells targeting these AML/LPC-associated antigens in AML patients and showed that antigen-specific T cell recognition and HLA class II immunopeptidome diversity impacts clinical outcome. Our results pave the way for implementation of AML/LPC-associated antigens for T cell-based immunotherapeutic approaches to specifically target and eliminate residual LPCs in AML patients.

2023-08-23 | GSE235080 | GEO

Acute myeloid leukemia immunopeptidome reveals HLA presentation of mutated nucleophosmin.

Project description: Not available

| S-EPMC6619824 | biostudies-literature

IFNγ modulates the immunopeptidome of triple negative breast cancer cells by enhancing and diversifying antigen processing and presentation

Project description:To identify potential T-cell targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine interferon-γ (IFNγ) on the transcriptome, proteome and immunopeptidome of the TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified a total of 84,131 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I and HLA-II alleles. Treatment with IFNγ resulted in a remarkable remoulding of the immunopeptidome, with only a 34% overlap between untreated and treated cells across the HLA-I immunopeptidome, and expression of HLA-II only on treated cells. IFNγ increased the overall number, diversity and abundance of the immunopeptidome, as well as the proportion of coverage of source antigens. The suite of peptides displayed under conditions of IFNγ treatment included many known tumour associated antigens, with the HLA-II repertoire sampling 265 breast cancer associated antigens absent from those sampled by HLA-I. Quantitative analysis of the transcriptome (10,248 transcripts) and proteome (6783 proteins) of these cells revealed 229 proteins and transcripts were commonly differentially expressed, most of which involved in downstream targets of IFNγ signalling including components of the antigen processing machinery such as tapasin and HLA. However, these changes in protein expression did not explain the dramatic modulation of the immunopeptidome following IFNγ treatment. These results demonstrate the high degree of plasticity in the immunopeptidome TNBC cells following cytokine stimulation and provide evidence that under pro-inflammatory conditions a greater variety of HLA-I and HLA-II vaccine targets are unveiled to the immune system. This has important implications for the development of personalised cancer vaccination strategies.

2021-04-01 | GSE163067 | GEO

The Proteogenomic Subtypes of Acute Myeloid Leukemia

Project description:Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. We performed a comprehensive proteogenomic analysis of bone-marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis included cytogenetic and mutation profiling, and RNA sequencing. This identified five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these subtypes were correlated with patient outcome, but none exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which was only captured in the proteome, was characterized by high expression of mitochondrial proteins and showed poor outcome, with reduced remission rate and shorter overall survival upon treatment with intensive induction chemotherapy. Functional analyses revealed that Mito-AML is metabolically wired towards stronger complex Idependent respiration and is more responsive to treatment with the BCL2-inhibitor venetoclax.

2022-03-08 | PXD028007 | Pride

RNA-Seq of Acute Myeloid Leukemia Cell lines with a 3q-aberration and Acute Myeloid Leukemia cell line controls

Project description:Using RNA deep sequencing we determined gene expression patterns and expression genotypes in Acute Myeloid Leukemia (AML) cell lines harboring a 3q-aberration. These cell lines specifically overexpress the gene EVI1 which plays a significant part in leukomogenesis. Additionally we RNA sequenced AML cell lines that overexpress EVI1 resulting from different genetic causes or do not express EVI1 at all.

2014-04-03 | E-MTAB-2225 | biostudies-arrayexpress

Nuclear proteomics in acute myeloid leukemia

Project description:The protein differences betweeen primary patient material from AML sufferers and normals was analysed using shotgun proteomics.

2019-10-14 | PXD002799 | Pride

Proteomics analysis for RBM17 in acute myeloid leukemia

Project description:Acute myeloid leukemia (AML) patients suffer from chemo-resistance, high relapse frequency, and low overall survival rate, outcomes driven by leukemic stem cells (LSCs). Understanding the molecular mechanisms that support these primitive leukemic cells is crucial for developing effective AML therapeutics. In the present study, we demonstrate that upregulation of the splicing factor RBM17 preferentially marks and sustains the primitive compartment of AML. We performed shotgun proteomics to characterize the proteome changes upon RBM17 knockdown in AMl cells. In addition, we used proteomics to analyze the proteome changes after knockdown of EIF4A2, a direct splicing substrate of RBM17 in AML cells.

2022-08-12 | PXD026780 | Pride

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