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HLA ligand profiles of primary renal cell carcinoma maintained in metastases

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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.

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Acknowledgments

We thank Lynne Yakes for critically reading the manuscript and Michael Bonin from the Microarray Facility Tübingen for helping with the gene expression analysis. This work was supported by the Deutsche Forschungsgemeinschaft. (DFG, SFB 685, GK 794) and the European Union (Cancer Immunotherapy, LSHC-CT-2006, 518234).

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Authors and Affiliations

  1. Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany

    Juliane Sarah Stickel, Andreas O. Weinzierl, Nina Hillen, Oliver Drews, Mathias M. Schuler, Hans-Georg Rammensee & Stefan Stevanović

  2. Clinic for Urology, University of Tübingen, 72076, Tübingen, Germany

    Jörg Hennenlotter & Arnulf Stenzl

  3. Institute for Clinical and Experimental Transfusion Medicine, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany

    Dorothee Wernet

  4. Department of Internal Medicine II, University of Tübingen, 72076, Tübingen, Germany

    Claudia A. Müller

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  1. Juliane Sarah Stickel
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Correspondence to Stefan Stevanović.

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Stickel, J.S., Weinzierl, A.O., Hillen, N. et al. HLA ligand profiles of primary renal cell carcinoma maintained in metastases. Cancer Immunol Immunother 58, 1407–1417 (2009). https://doi.org/10.1007/s00262-008-0655-6

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  • DOI: https://doi.org/10.1007/s00262-008-0655-6

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