Intraperitoneal oxaliplatin administration inhibits the tumor immunosuppressive microenvironment in an abdominal implantation model of colon cancer
Intraperitoneal oxaliplatin administration inhibits the tumor immunosuppressive microenvironment in an abdominal implantation model of colon cancer
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DOI：
10.3892/mmr.2018.9219
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发表时间：
2018-08-01
影响因子：
3.4
通讯作者：
Chen, Xin-Chuan
中科院分区：
文献类型：
--
作者：
Gou, Hong-Feng;Zhou, Lei;Chen, Xin-Chuan
近年来的研究表明，某些化疗药物可以通过清除和灭活免疫抑制细胞来增强抗肿瘤免疫。奥沙利铂（OXP）通过增加癌细胞的免疫原性诱导免疫原性细胞死亡。然而，OXP对肿瘤免疫抑制微环境的影响仍不清楚。本研究的目的是通过腹膜内（i. p.）在结肠癌的腹部植入模型中施用OXP，并测试肿瘤免疫微环境以观察OXP是否影响局部免疫抑制细胞群。接种CT 26细胞建立腹腔转移模型。评价OXP的抗肿瘤效果和肿瘤免疫微环境。收获小鼠的肿瘤和脾脏用于流式细胞术分析。流式细胞术检测CD-8 + CD 69 + T细胞、调节性T细胞、CD 11b +F4/80（high）巨噬细胞和髓源性抑制细胞（MDSC）。在腹腔转移模型中，OXP的体内腹膜内给药抑制肿瘤生长。此外，观察到OXP增加肿瘤中肿瘤浸润的活化的CD 8 + T细胞，减少肿瘤中的CD 11b +F4/80 high巨噬细胞，并减少脾脏中的MDSC。这些结果表明，单独腹腔注射OXP可抑制肿瘤细胞生长，并通过消除免疫抑制细胞诱导抗肿瘤免疫刺激微环境。
Recent studies have demonstrated that some chemotherapeutic drugs can enhance antitumor immunity by eliminating and inactivating immunosuppressive cells. Oxaliplatin (OXP) induces immunogenic cell death by increasing the immunogenicity of cancer cells. However, the effects of OXP on the tumor immunosuppressive microenvironment remain unclear. The aim of the present study was to evaluate the antitumor activity of OXP by intraperitoneal (i.p.) administration in an abdominal implantation model of colon cancer and tested the tumor immune microenvironment to observe whether OXP affects the local immune inhibitory cell populations. Abdominal metastasis models were established by inoculation of CT26 cells. The antitumor efficacy of OXP and the tumor immune microenvironment were evaluated. The tumors and spleens of mice were harvested for flow cytometric analysis. Cluster of differentiation (CD)-8+CD69+ T cells, regulatory T cells (Tregs), CD11b+F4/80(high) macrophages and myeloid-derived suppressor cells (MDSCs) were evaluated by flow cytometric analysis. In vivo i.p. administration of OXP inhibited tumor growth in the abdominal metastasis model. Furthermore, OXP was observed to increase tumor-infiltrating activated CD8+ T cells in tumors, decrease CD11b+F4/80high macrophages in tumors and decrease MDSCs in the spleen. These results suggested that i.p. administration of OXP alone may inhibit tumor cell growth and induce the antitumor immunostimulatory microenvironment by eliminating immunosuppressive cells.