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Mapping the HLA ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation

ABSTRACT: Immunopeptidome analysis of colorectal adenocarcinoma tissues as well as adjacent benign tissues was performed to characterize the natural HLA class I and class II presented ligandome represented in the context of malignancy as well as in benign tissue of the colon.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Michael Ghosh

LAB HEAD: Hans-Georg Rammensee

PROVIDER: PXD009602 | Pride | 2019-03-12

REPOSITORIES: Pride

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			Action	DRS
	UPN_10_HLA-class_II_CRC_malignant_Rep1.msf	Msf
	UPN_10_HLA-class_II_CRC_malignant_Rep1.raw	Raw
	UPN_10_HLA-class_II_CRC_malignant_Rep2.msf	Msf
	UPN_10_HLA-class_II_CRC_malignant_Rep2.raw	Raw
	UPN_10_HLA-class_II_NMT_benign_Rep1.msf	Msf

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Publications

Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation.

Löffler Markus W MW Kowalewski Daniel J DJ Backert Linus L Bernhardt Jörg J Adam Patrick P Schuster Heiko H Dengler Florian F Backes Daniel D Kopp Hans-Georg HG Beckert Stefan S Wagner Silvia S Königsrainer Ingmar I Kohlbacher Oliver O Kanz Lothar L Königsrainer Alfred A Rammensee Hans-Georg HG Stevanović Stefan S Haen Sebastian P SP

Cancer research 20180522 16

Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue. Mass spectrometry i ...[more]

PMID: 29789417

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A Non-interventional Clinical Trial Assessing Immune Responses After Radiofrequency Ablation of Liver Metastases From Colorectal Cancer

Project description:HLA ligandome analysis of colorectal adenocarcinoma tissues obtained from liver metastases (mCRC) as well as adjacent non-malignant liver tissues was performed to characterize the natural HLA class I and class II presented ligands on both mCRC and adjacent liver tissue.

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TOFIMS mass spectrometry-based immunopeptidomics refines tumor antigen identification

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The HLA-ligandome of oropharyngeal squamous cell carcinomas reveals shared tumor-exclusive peptides for semi-personalized vaccination

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2023-02-27 | PXD033383 | Pride

The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy

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The HLA-Ligand-Atlas. A resource of natural HLA ligands presented on benign tissues

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2021-04-16 | PXD019643 | Pride

Multi-omics discovery of exome-derived neoantigens in hepatocellular carcinoma

Project description:HLA class I ligandome dataset obtained from hepatocellular carcinoma (HCC) as well as corresponding adjacent benign liver tissue (n=16) characterizing respective HLA immunoprecipitates. Additionally, from a subset of the mentioned HCC/ adjacent benign liver samples datasets gained from shotgun protein identification, comprising HCC as well as adjacent benign liver tissue (n=7) are provided. Further, for one patient shotgun protein identification was also performed in serum (blood) samples obtained after HCC recurrence.

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The immunopeptidomic landscape of ovarian carcinoma

Project description:Immunopeptidome analysis of ovarian carcinoma tissues was performed to characterize the HLA class I and class II presented ligandome of this malignancy.

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The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell–based immunotherapy

Project description:Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma-associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide-specific, preexisting CD8+ T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell–based immunotherapy of MM.

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