Department of Abdominal Cancer, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Department of Abdominal Cancer, Cancer Center, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Mol Med Rep. 2018 Aug;18(2):2335-2341. doi: 10.3892/mmr.2018.9219. Epub 2018 Jun 25.
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+F4/80high 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.
最近的研究表明，一些化疗药物可以通过消除和失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尚不清楚。本研究旨在通过腹腔（i.p.）给予奥沙利铂在结肠癌腹腔种植模型中评估其抗肿瘤活性，并检测肿瘤免疫微环境，观察 OXP 是否影响局部免疫抑制细胞群体。通过接种 CT26 细胞建立了腹部转移模型。评估了 OXP 的抗肿瘤功效和肿瘤免疫微环境。采集小鼠的肿瘤和脾脏进行流式细胞术分析。通过流式细胞术分析评估 CD8+CD69+T 细胞、调节性 T 细胞（Tregs）、CD11b+F4/80high 巨噬细胞和髓系来源的抑制细胞（MDSCs）。体内 i.p.给予 OXP 抑制了腹部转移模型中的肿瘤生长。此外，观察到 OXP 增加了肿瘤中浸润的激活 CD8+T 细胞，减少了肿瘤中的 CD11b+F4/80high 巨噬细胞，并减少了脾脏中的 MDSCs。这些结果表明，单独腹腔内给予 OXP 可能通过消除免疫抑制细胞来抑制肿瘤细胞生长并诱导抗肿瘤免疫刺激微环境。
