| In this study, the therapeutic effect and anti-tumor immunity induced by the alternate cooling and heating was investigated using 4T1 murine mammary carcinoma, a common model of human metastatic breast cancer. The treatment was performed at the time when metastasis was well established and surgical resection of primary tumor could not cure the mice. However, after the alternate treatment, fifteen of seventeen mice were cured while neither heat nor cooling alone could achieve the similar effect. The same protocol could hardly cure nude mice with 4T1 tumor of the same stage and histological analyses showed that viable cells existed in the tumor debris after the treatment, indicating that direct killing effect was not the only therapeutic mechanism.Further investigation found rejection of tumor upon re-challenge, and anti-tumor immune response was studied. Stronger cytotoxicity T-lymphocyte (CTL) and Th1 cytokines response were observed than that after surgical resection. Moreover, the infiltration of immunocytes into the tumor area greatly increased. The results showed that the alternate cooling and heat could stimulate anti-tumor immunologic response in vivo and the underlying mechanisms will be further investigated in the near future. |
