Open AccessModulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model
Author(s) -
Shimizu Taro,
Abu Lila Amr S.,
Nishio Miho,
Doi Yusuke,
Ando Hidenori,
Ukawa Masami,
Ishima Yu,
Ishida Tatsuhiro
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13305
Subject(s) - immune system , oxaliplatin , liposome , tumor microenvironment , immunity , cancer research , cytotoxic t cell , lewis lung carcinoma , immunology , pharmacology , medicine , chemistry , cancer , colorectal cancer , in vitro , metastasis , biochemistry
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 PEG ylated 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 PEG ylated 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 CD 8 + 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.