Gou Hong-Feng, Huang Juan, Shi Hua-Shan, Chen Xin-Chuan, Wang Yong-Sheng
Department of Abdominal Cancer, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Department of Head and Neck Cancer, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
PLoS One. 2014 Jan 21;9(1):e85789. doi: 10.1371/journal.pone.0085789. eCollection 2014.
Combination of immunotherapy and chemotherapy has shown promise for cancer. Interleukin-7 (IL-7) can potentially enhance immune responses against tumor, while oxaliplatin (OXP), a platinum-based drug, can promote a favorable immune microenvironment and stimulate anticancer immune responses. We evaluated the anti-tumor activity of IL-7 combining OXP against a murine colon carcinoma in vitro and in vivo and studied the tumor immune microenvironment to investigate whether the combined treatment affects on the local immune cell populations. Utilizing lung and abdomen metastasis models by inoculation of CT26 mice colon cancer cells, we evaluated the anti-tumor efficacy of combining IL-7 and OXP in mice models. Tumor immune microenvironment was evaluated by flow cytometric analysis and immunohistochemical staining. Our study showed that the in vivo administration of IL-7 combined with OXP markedly inhibited the growth of tumors in lung and abdomen metastasis models of colon cancer. IL-7 alone had no effect on tumor growth in mice and IL-7 did not alter cell sensitivity to OXP in culture. The antitumor effect of combining IL-7 and OXP correlated with a marked increase in the number of tumor-infiltrating activated CD8+ T cells and a marked decrease in the number of regulatory T (Treg) cells in spleen. Our data suggest that OXP plus IL-7 treatment inhibits tumor cell growth by immunoregulation rather than direct cytotoxicity. Our findings justify further evaluation of combining IL-7 and chemotherapy as a novel experimental cancer therapy.
免疫疗法与化疗的联合应用已显示出对癌症治疗的前景。白细胞介素-7（IL-7）可能增强针对肿瘤的免疫反应，而奥沙利铂（OXP），一种铂类药物，可促进良好的免疫微环境并刺激抗癌免疫反应。我们评估了IL-7联合OXP对小鼠结肠癌的体外和体内抗肿瘤活性，并研究了肿瘤免疫微环境，以调查联合治疗是否影响局部免疫细胞群体。通过接种CT26小鼠结肠癌细胞建立肺和腹部转移模型，我们评估了IL-7与OXP联合在小鼠模型中的抗肿瘤疗效。通过流式细胞术分析和免疫组织化学染色评估肿瘤免疫微环境。我们的研究表明，在结肠癌肺和腹部转移模型中，体内给予IL-7联合OXP可显著抑制肿瘤生长。单独使用IL-7对小鼠肿瘤生长没有影响，并且IL-7在培养中不会改变细胞对OXP的敏感性。IL-7与OXP联合的抗肿瘤作用与肿瘤浸润活化CD8 + T细胞数量的显著增加以及脾脏中调节性T（Treg）细胞数量的显著减少相关。我们的数据表明，OXP加IL-7治疗通过免疫调节而非直接细胞毒性抑制肿瘤细胞生长。我们的研究结果证明进一步评估IL-7与化疗联合作为一种新型实验性癌症治疗方法是合理的。
