The synergistic antitumor effect of arsenic trioxide combined with cytotoxic T cells in pulmonary metastasis model of colon cancer

// Lei Wang 1, 2 , Wentao Liang 3 , Na Peng 4 , Xiang Hu 1 , Yingxin Xu 3 and Zhong Liu 1 1 Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China 2 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China 3 Institute of General Surgery, Chinese PLA General Hospital, Beijing 100853, China 4 Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, China Correspondence to: Zhong Liu, email: surgerydoctor@sina.com Yingxin Xu, email: xyx20151026@sina.com Keywords: arsenic trioxide; cytotoxic T cells; regulatory T cell; colon cancer; adoptive T cell therapy Received: November 01, 2016     Accepted: November 16, 2017     Published: November 30, 2017 ABSTRACT Adoptive T cell therapy, including cytotoxic T lymphocytes (CTLs), represents a promising non-toxic anticancer strategy. The effects of this therapy can be impaired by tumor-infiltrated regulatory T cells (Tregs). Autologous murine CTLs acquired using cryopreservation exhibited a cytotoxic effect equivalent to that of conventional CTLs. The killing activity of CTLs was enhanced significantly using arsenic trioxide (ATO), accompanied by reduction in Tregs in vitro . Results using a pulmonary metastasis model of colon cancer indicated that compared with the control group, ATO group, and CTLs group, metastatic node number decreased significantly ( p <0.001, p <0.001, p <0.001, respectively) and survival time was prolonged ( p <0.001, p =0.669, p =0.158, respectively) in the ATO plus CTLs group. The number of infiltrated Foxp3+ Tregs decreased in the tumor center, but increased in the peri-tumor tissue. Our results indicate that this approach represents a practical protocol for acquiring autologous CTLs and a feasible strategy that uses a synergistic combination of ATO plus CTLs to treat pulmonary metastases of colon cancer.