Oncotarget

Research Papers:

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

Lei Wang, Wentao Liang, Na Peng, Xiang Hu, Yingxin Xu and Zhong Liu _

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Oncotarget. 2017; 8:109609-109618. https://doi.org/10.18632/oncotarget.22757

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Abstract

Lei Wang1,2, Wentao Liang3, Na Peng4, Xiang Hu1, Yingxin Xu3 and Zhong Liu1

1Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China

2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China

3Institute of General Surgery, Chinese PLA General Hospital, Beijing 100853, China

4Zhongnan 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: [email protected]

Yingxin Xu, email: [email protected]

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.


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