Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. We analyzed the expression and immunogenicity of different tumor-associated antigens (TAAs) in ccRCC patients. We found expression of MAGE-A9 and NY-ESO-1 and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET and RGS-5 in many of the 23 primary ccRCC tumor samples tested. Subsequently, we investigated the presence of CD8+ T cells specific for previously identified HLA-A2-restricted peptides derived from the relevant TAAs in the blood of HLA-A2+ patients. We found spontaneous responses towards Cyclin D1 in 5 out of 6 patients with Cyclin D1-positive tumors. Cyclin D1-specific CD8+ T cells secreted TNF-α, IFN-γ, and IL-2 and degranulated, suggesting the presence of polyfunctional tumor-specific CD8+ T cells in the blood of patients with primary ccRCC. The frequent occurrence of Cyclin D1 overexpression in ccRCC specimens (43%) and the frequent detection of functional Cyclin D1-specific T cells in those patients (83%) makes Cyclin D1 an interesting target for future immunotherapeutic strategies.
- Received August 5, 2013.
- Accepted August 13, 2013.
- Copyright © 2013, American Association for Cancer Research.