Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

HLA ligand profiles of primary renal cell carcinoma maintained in metastases.sue

ABSTRACT: In recent years, several approaches have been taken in the peptide-based immunotherapy of metastatic renal cell carcinoma (RCC), although little is known about HLA presentation on metastases compared to primary tumor and normal tissue of RCC. In this study we compared primary tumor, normal tissue and metastases with the aim of identifying similarities and differences between these tissues. We performed this comparison for two RCC patients on the level of the HLA ligandome using mass spectrometry and for three patients on the level of the transcriptome using oligonucleotide microarrays. The quantitative results show that primary tumor is more similar to metastasis than to normal tissue, both on the level of HLA ligand presentation and mRNA. We were able to characterize a total of 142 peptides in the qualitative analysis of HLA-presented peptides. Six of them were significantly overpresented on metastasis, among them a peptide derived from CD151; fourteen were overpresented on both primary tumor and metastasis compared to normal tissue, among them an HLA ligand derived from tumor protein p53. Thus, we could demonstrate that peptide-based immunotherapy might affect tumor as well as metastasis of RCC, but not healthy kidney tissue. Furthermore we were able to identify several peptides derived from tumor-associated antigens that are suitable for vaccination of metastatic RCC. Three clear cell renal cell carcinomas including autologous normal tissue and autologous metastasis were analyzed. This dataset is part of the TransQST collection.

ORGANISM(S): Homo sapiens

SUBMITTER: Andreas Weinzierl

PROVIDER: E-GEOD-12606 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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HLA ligand profiles of primary renal cell carcinoma maintained in metastases.

Stickel Juliane Sarah JS Weinzierl Andreas O AO Hillen Nina N Drews Oliver O Schuler Mathias M MM Hennenlotter Jörg J Wernet Dorothee D Müller Claudia A CA Stenzl Arnulf A Rammensee Hans-Georg HG Stevanović Stefan S

Cancer immunology, immunotherapy : CII 20090201 9

In recent years, several approaches have been taken in the peptide-based immunotherapy of metastatic renal cell carcinoma (RCC), although little is known about HLA presentation on metastases compared to primary tumor and normal tissue of RCC. In this study we compared primary tumor, normal tissue and metastases with the aim of identifying similarities and differences between these tissues. We performed this comparison for two RCC patients on the level of the HLA ligandome using mass spectrometry ...[more]

PMID: 19184600

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Project description:Various cancer immunotherapies rely on the T cell recognition of peptide antigens presented on human leukocyte antigens (HLA). However, the identification and selection of naturally presented peptide targets for the development of personalized as well as off-the-shelf immunotherapy approaches remains challenging. Here, we introduce the open-access Peptides for Cancer Immunotherapy Database (PCI-DB, https://pci-db.org/), a comprehensive resource of immunopeptidome data originating from various malignant and benign primary tissues that provides the research community with a convenient tool to facilitate the identification of peptide targets for immunotherapy development. The PCI-DB includes > 6.6 million HLA class I and > 3.4 million HLA class II peptides from over 40 tissue types and cancer entities analyzed uniformly using high-sensitive nf-core bioinformatics pipelines and applying a global peptide false discovery rate (FDR) approach. First application of the database provided insights into the representation of cancer-testis antigens (CTA) across malignant and benign tissues and enabled the identification and characterization of the cross-tumor entity and entity-specific tumor-associated antigens as well as naturally presented neoepitopes from frequent cancer mutations. Further, we used the PCI-DB to design personalized peptide vaccines for two patients suffering from metastatic cancer. PCI-DB enabled the composition of both a multi-peptide vaccine comprising non-mutated, highly frequent tumor-associated antigens matching the immunopeptidome of the individual patient´s tumor and a neoepitope-based vaccine matching the mutational profile of the cancer patient. Both vaccine approaches induced potent and long-lasting T-cell responses, accompanied by long-term survival of these advanced cancer patients. In conclusion, the PCI-DB provides a highly versatile tool to broaden the understanding of cancer-related antigen presentation and, ultimately, supports the development of novel immunotherapies.

Dataset Information

HLA ligand profiles of primary renal cell carcinoma maintained in metastases.sue

Publications

HLA ligand profiles of primary renal cell carcinoma maintained in metastases.

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