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

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

doi:10.18632/oncotarget.22757

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.

Highlights

Immunotherapy represents a promising non-toxic anticancer strategy [1, 2], but the various treatment modalities used so far have resulted in only limited and sporadic success [3, 4]
Our results indicate that this approach represents a practical protocol for acquiring autologous cytotoxic T lymphocytes (CTLs) and a feasible strategy that uses a synergistic combination of arsenic trioxide (ATO) plus CTLs to treat pulmonary metastases of colon cancer
We assessed the capacity of cryopreserved lymphocytes to produce cytokine-induced killer (CIK) cells in vitro and found that there were no differences in the ratio of regulatory T cells (Tregs) (Figure 1D), the levels of IFN-γ extracted from their supernatants (Figure 1E), or cytotoxicity (Figure 1F) between CIK and the cryopreserved CIK cells

Summary

Introduction

Immunotherapy represents a promising non-toxic anticancer strategy [1, 2], but the various treatment modalities used so far have resulted in only limited and sporadic success [3, 4]. The exact mechanism of successful therapies is unclear, but is often attributed to the reduction of regulatory T cells (Tregs) [5,6,7]. A previous study suggested that ATO treatment could deplete Tregs [14], www.impactjournals.com/oncotarget and we confirmed this mechanism in our previous study [19]. Based on these two studies, we investigated the effects of a combined treatment of ATO and adoptive T cells using a lung metastasis model of mouse colon cancer

Methods

Results

Conclusion