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Mol Med Rep. 2018 Aug;18(2):2335-2341. doi: 10.3892/mmr.2018.9219. Epub 2018 Jun 25.

Intraperitoneal oxaliplatin administration inhibits the tumor immunosuppressive microenvironment in an abdominal implantation model of colon cancer.

Author information

1
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.
2
Department of Abdominal Cancer, Cancer Center, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
3
Department of Hematology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Abstract

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.

PMID:
29956798
DOI:
10.3892/mmr.2018.9219
[Indexed for MEDLINE]

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