ИСТИНА

Early diagnosis remains the main strategy for reducing morbidity and mortality in renal cell carcinoma (RCC) patients, while high immunogenicity of these tumors renders cancer-associated autoantigens as attractive diagnostical biomarkers and promising targets for immunotherapy. In the present study we explored renal cell carcinoma autoantigenic repertoire by means of Serological Proteome Analysis (SEPRA) using A.704 and RCC68 cell lines and RCC patients/healthy donors’ sera as primary (auto)antibody sources for two-dimensional Western-blot analysis. Proteins demonstrating differential immunoreactivity between groups of RCC patients and healthy donors were identified using LC-MS/MS analysis. Annexin A4 (ANXA4) was one of the most promising candidates and was selected for further examination of in vitro effector CD8+ T-cell response against five HLA-B (B13, B15, B18 and B27) - restricted ANXA4 peptides previously identified as a part of RCC-associated HLA class I peptidome. In a first screening, we were able to detect spontaneous effector CD8+ T-cell response against 2 HLA-B15-restricted peptides in 1 out of 7 HLA-B15+ carriers suffering from RCC. Moreover, ANXA4 was overexpressed in malignant versus normal kidney tissue (Oncomine database). Taken together, we identified a number of candidate autoantibody biomarkers of RCC and propose ANXA4 as a novel tumor associated antigen.