Immunologic response to primary cryoablation of high-risk prostate cancer

Abstract

Objective: To assess whether a specific cytotoxic T-cell response can be induced in patients with prostate cancer after cryoablation. Material and Methods: Twenty Patients with high-risk prostate cancer underwent cryoablation. Blood was sampled prior to, 4 and 8 weeks after treatment. Serum cytokine levels were analyzed by ELISA, and the Th1/Th2 ratio was estimated from the IFN-γ/IL-4 ratio. Peripheral blood mononuclear cells (PBMC) were stimulated with autologous prostate cancer-derived protein lysates, and frequency of tumor-specific T-cells was tested ex vivo in an IFN-γ ELISPOT assay. To assess cytolytic activity, T-cells were co-incubated with human prostate cancer cells, LNCaP, or with renal cancer cells, GRC-1, and release of cytosolic adenylate kinase was measured by a luciferase assay. Result: 4 weeks after cryoablation significantly higher levels of TNF-α and IFN-γ were observed compared to before treatment, and to 8 weeks after treatment. No changes in IL-4 or IL-10 were observed. The Th1/Th2 ratio (10.47 ± 0.80), 4 weeks after treatment, was increased compared to before treatment (3.98 ± 0.45), but decreased 8 weeks later (7.65 ± 0.64). Tumor-specific T-cell responses were evident after cryosurgery in PBMC. Cytolytic activity against LNCaP was increased 4 weeks after treatment compared to before treatment (594.49 ± 154.84 versus 4.20 ± 0.68, P < 0.01), but was decreased 8 weeks later (79.70 ± 18.73). No response was found in cytolytic activity against GRC-1. Conclusion: Cryoablation of prostate cancer can improve tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity. However, the response is not sufficiently maintained to prevent cancer relapse.