Data from Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

Abstract

<div>Abstract<p>Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of <i>MAGE-A9</i> and <i>NY-ESO-1</i> in 36% and 55% of samples, respectively, and overexpression of <i>PRAME</i>, <i>RAGE-1</i>, <i>CA-IX</i>, <i>Cyclin D1</i>, <i>ADFP</i>, <i>C-MET</i>, and <i>RGS-5</i> in many of the tumor samples. We analyzed the blood of patients with HLA-A2<sup>+</sup> ccRCC for the presence of CD8<sup>+</sup> T cells specific for TAA-derived HLA-A2–restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with <i>Cyclin D1</i>–positive tumors. Cyclin D1–specific CD8<sup>+</sup> T cells secreted TNF-α, IFN-γ, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8<sup>+</sup> T cells in the blood of these patients with ccRCC. The high frequency (43%) of <i>Cyclin D1</i> overexpression and the presence of functional cyclin D1–specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies. <i>Cancer Immunol Res; 1(5); 288–95. ©2013 AACR</i>.</p></div>