徳島大学 教育・研究者情報データベース(EDB)

1. 清水 太郎

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2. (英) Amr Selim Ahmed Ali Abu Lila / (読) あむる せりむ あはめど あり あぶ りら

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3. (英) Nishio Miho / (日) 西尾 美穂 / (読) にしお みほ

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4. (英) Doi Yusuke / (日) 土井 祐輔 / (読) どい ゆうすけ

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5. 安藤 英紀([徳島大学.大学院医歯薬学研究部.薬学域.薬科学部門.生命薬学系.薬物動態制御学])

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6. 鵜川 真実

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7. 異島 優

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8. 石田 竜弘([徳島大学.大学院医歯薬学研究部.薬学域.薬科学部門.生命薬学系.薬物動態制御学]/[徳島大学.大学院医歯薬学研究部.薬学域.連携研究部門(薬学域).寄附講座系(薬学域).がん細胞と代謝学]/[徳島大学.大学産業院])

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(英) Modulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model

(英) 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.