Transcription profiling of human renal cell carcinoma patients (2 individuals) comparison of primary tumor, metastatic and normal tissues reveals the close relation of metastatic HLA and mRNA profiles with primordial tumor tissue

In recent years, several approaches in peptide-based immunotherapy for metastatic renal cell carcinoma (RCC) were made, 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 to identify similarities and differences among 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 HLA ligand presenting level and the mRNA level. In the qualitative analysis of HLA presented peptides, we could identify a total of 144 peptides, of which 9 were significantly overpresentated on metastasis and 17 were overpresentated on primary tumor and metastasis compared to normal tissue. Thus, we could show that a peptide-based immunotherapy has the possibility to affect tumor and metastasis of RCC but not the healthy kidney tissue. Furthermore, we could identify several peptides from tumor-associated antigens, suitable for vaccination of metastatic RCC. Experiment Overall Design: Three clear cell renal cell carcinomas including autologous normal tissue and autologous metastasis were analyzed.