Cryosurgery for Treatment of Subcutaneously Xenotransplanted Tumors in Rats and its Effect on Cellular Immunity

Abstract

Cryosurgery has shown encouraging therapeutic effects on some solid tumors but its effect on the cellular immunity remains unclear. We developed a subcutaneously xenotransplanted tumor model in SD rats to directly evaluate the immune response by detecting the serum cytokine levels, T-cell responses to tumor derived antigens, and the cytolytic activity of peripheral blood mononuclear cells against the W256 cancer line with apoptosis of cells being detected using TUNEL method. 66 SD rats were divided into 2 groups with group A having 36 rats and group B having 30 rats. 30 rats in group B were equally divided into 3 groups, tumor group B, cryosurgery group B and surgery group B, with 10 rats each. 36 rats in group A were equally divided into 2 groups, cryosurgery group A and tumor group A and treatment was done accordingly. The results showed that cryosurgery induced not only destruction of the tumor cells but also cell apoptosis around the cryosurgery foci. The apoptosis ratio reached the peak 12 h after cryosurgery, with an apoptosis rate of (68.28 ± 7.85)%. Compared with surgical resection that caused significant reduction in CD3+ and CD4+ cell percentages, cryosurgery resulted in significantly increased percentages of CD3+ and CD4+ cells (P < 0.05) with a relative increase of the CD4+/CD8+ cell ratio. However, sIL-2R level of peripheral blood of rats in cryosurgery group which decreased more rapidly than that in surgery group over time was significantly different 3 and 5 weeks after treatment compared to surgery group (P < 0.01). Moreover, cytotoxicity of mononuclear cell was significantly enhanced after cryosurgery, which is significantly higher in cryosurgery group (P = 0.05). These results demonstrate that in addition to tumor cell destruction, cryosurgery also results in enhanced cellular immunity and antitumor immune response of the rats with subcutaneously xenotransplanted tumor, suggesting the great potential of argon-helium cryosurgery in clinical management.