Wang Lei, Liang Wentao, Peng Na, Hu Xiang, Xu Yingxin, Liu Zhong
Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China.
Oncotarget. 2017 Nov 30;8(65):109609-109618. doi: 10.18632/oncotarget.22757. eCollection 2017 Dec 12.
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 . 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 (<0.001, <0.001, <0.001, respectively) and survival time was prolonged (<0.001, =0.669, =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.
过继性T细胞疗法，包括细胞毒性T淋巴细胞（CTL），是一种很有前景的无毒抗癌策略。肿瘤浸润调节性T细胞（Treg）会削弱这种疗法的效果。使用冷冻保存获得的自体小鼠CTL表现出与传统CTL相当的细胞毒性作用。使用三氧化二砷（ATO）可显著增强CTL的杀伤活性，并伴有Treg数量减少。使用结肠癌肺转移模型的结果表明，与对照组、ATO组和CTL组相比，ATO加CTL组的转移结节数量显著减少（分别为<0.001、<0.001、<0.001），生存时间延长（分别为<0.001、=0.669、=0.158）。肿瘤中心浸润的Foxp3 + Treg数量减少，但肿瘤周围组织中的数量增加。我们的结果表明，这种方法是获取自体CTL的实用方案，也是使用ATO加CTL协同组合治疗结肠癌肺转移的可行策略。
