Modulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model.

Abstract

Immune modulation of the tumor microenvironment has been reported to participate in the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l-OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l-OHP in murine colorectal carcinoma-bearing mice through permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune-modulatory properties of liposomal l-OHP and/or free l-OHP to the overall antitumor efficacy was not elucidated. In the present study, therefore, we investigated the effect of liposomal encapsulation of l-OHP within PEGylated liposomes on the antitumor immunity in both immunocompetent and immunodeficient mice. Liposomal l-OHP significantly suppressed the growth of tumors implanted in immunocompetent mice, but not in immunodeficient mice. In immunocompetent mice, liposomal l-OHP increased the tumor MHC-1 level and preserved antitumor immunity through decreasing the number of immune suppressor cells, including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages, which collectively suppress CD8+ T cell-mediated tumor cells killing. In contrast, free l-OHP ruined antitumor immunity. These results suggest that the antitumor efficacy of liposomal l-OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l-OHP, and on the other hand, to its direct cytotoxic effect on tumor cells.

• Authors: Taro Shimizu, Amr S Abu Lila, Miho Nishio, Yusuke Doi, Hidenori Ando, Masami Ukawa, Yu Ishima, Tatsuhiro Ishida
• Journal: Cancer science (Cancer Sci) Vol. 108 Issue 9 Pg. 1864-1869 (Sep 2017) ISSN: 1349-7006 [Electronic] England
• PMID: 28643902 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antineoplastic Agents
• Histocompatibility Antigens Class I
• Immunologic Factors
• Liposomes
• Organoplatinum Compounds
• Oxaliplatin

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Cell Line, Tumor
• Colorectal Neoplasms (drug therapy, immunology)
• Drug Screening Assays, Antitumor
• Histocompatibility Antigens Class I (metabolism)
• Immunologic Factors (administration & dosage)
• Liposomes
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin