Tumor Suppressor Gene P29ing4 is Overexpressed and Induces a CD8 T EffectorCell Response in Human Renal Cell Carcinoma

Objective: ING1 and ING4 are identified as candidate tumor suppressor genes acting in regulation of DNA damage responses and apoptosis through modulation of p53. Their defective function promotes tumor growth in melanoma and breast cancer. Our aim was to determine the overexpression of relevant p33ING1b and p29ING4 isoforms in patients with Renal Cell Cancer (RCC). Methods: Peripheral Blood Mononuclear Cells (PBMCs) from tumor patients (Robson stage I-IV) were stimulated with overlapping peptides of p33ING1b/p29ING4 and results were compared with expression profiles in primary tumors. Results: Early-stage and late-stage tumors demonstrated upregulated ING-isoform gene and protein expression. Early cancers were characterized by increased CD8 and IFN-γ protein and gene expression. Significant p33ING1b and p29ING4 tumor-specific CD8 T effector cell responses from PBMCs of the analyzed tumor patients were observed. Interestingly, peptide sequences p33ING1b (aa259-268) and p29ING4 (aa149-158) elicited significant IFN-γ responses indicative for anti-tumor immune responses while IL-2 responses were detected only for p29ING4 (aa149-158), suggesting inducible T effector cell responses. Conclusion: T effector cell analysis against p29ING4 (aa149-158) suggests a promising candidate for in vivo induction of tumor-reactive CD8 T effector cells in patients with renal cell cancer.