HLA ligand profiles of primary renal cell carcinoma maintained in metastases.
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.
Stickel
Juliane Sarah
JS
Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany. Juli-stickel@gmx.de
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
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism* / Q000556:secondary; D020869:Gene Expression Profiling; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D013058:Mass Spectrometry; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments
D014408:Biomarkers, Tumor; D006680:HLA Antigens; D008024:Ligands; D010446:Peptide Fragments