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• W2894773808 abstract "Current therapy of ccRCC is commonly constrained by low response rates and frequent resistance against administered drugs. In recent years, drug discovery is focusing on the positive modulation of the immune system. The lately approved checkpoint ab nivolumab for treatment of ccRCC is the first drug in the upcoming era of immunotherapy. Being an immunogenic tumor entity, specific immunotherapies have the potential to increase the anti-cancer response with lower side effects.To identify suitable targets for a specific immunotherapy a comprehensive analysis on the HLA ligandome of 58 ccRCC samples and corresponding adjacent benign tissues was conducted by LC-MS/MS and compared to an additional in-house database of benign immunopeptidomes. TUMAPs were selected according to several evaluations focusing on tumor exclusivity, quantitative expression and HLA restriction as well as the biological role of the source antigens. Overall, 26 peptides from six HLA alleles were selected and screened for their immunogenicity in CD8+ T cell priming experiments, with 19 peptides exhibiting immune recognition. This set of peptides can be considered for future specific immunotherapeutic approaches.HLA-C as well as HLA-E and HLA-G molecules possess important roles in both the innate and adaptive immunity with different immunomodulatory functions. However, the uncovering of the peptide motifs received insufficient attention until recent data from in vitro binding experiments for HLA-C allotypes. For this purpose, the characterization of the binding specificities of the most frequent HLA-C allotypes as well as HLA-E and HLA-G were accomplished by LC-MS/MS-based identification of naturally processed and presented HLA ligands from monoallelic C1R transfectants. HLA-C allotypes display anchors in the B or C pocket (position 2 or 3 within the peptide) and a less variable anchor in pocket F (C-terminal position within the peptide). Overall, 20,156 HLA-C ligands were identified. For HLA-E the previously reported small ligand repertoire could be confirmed with five identified ligands, whereas a large ligand repertoire for HLA-G (2258 ligands) could be unveiled with anchor positions 3 and 9 and an auxiliary anchor at position 1. The data was utilized to establish SYFPEITHI matrices for epitope prediction and for peptide assignment to the correct HLA. Especially for HLA-G the number of HLA ligands could be tremendously increased from three prior known HLA ligands within the IEDB database to more than 2000 HLA ligands.; Die gegenwartige Therapie vom klarzelligem Nierenzellkarzinom ist, sowohl durch eine niedrige Ansprechrate als auch durch die haufig auftretenden Resistenzen gegenuber der angewandten Medikation begrenzt. Dies ist ein Grund weshalb der Fokus immer weiter in Richtung Modulation des Immunsystems gesetzt wird. Der kurzlich fur ccRCC zugelassene Checkpoint-Inhibitor-Antikorper Nivolumab ist das erste Medikament der bevorstehenden Ara der Immuntherapie. Spezifische Immuntherapien haben aufgrund der Immunogenitat von ccRCC das…" @default.
• W2894773808 created "2018-10-12" @default.
• W2894773808 creator A5010250023 @default.
• W2894773808 date "2018-08-28" @default.
• W2894773808 modified "2023-09-24" @default.
• W2894773808 title "The immunopeptidomic landscape of clear cell renal cell carcinoma: identification and characterization of T-cell epitopes for immunotherapeutic approaches" @default.
• W2894773808 doi "https://doi.org/10.15496/publikation-25223" @default.
• W2894773808 hasPublicationYear "2018" @default.
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