The liposome of trehalose dimycolate extracted from M. bovis BCG induces antitumor immunity via the activation of dendritic cells and CD8+ T cells

被引：18

作者：

Shiga, Masanobu ^{[1
]}

Miyazaki, Jun ^{[2
]}

Tanuma, Kozaburo ^{[1
]}

Nagumo, Yoshiyuki ^{[1
]}

Yoshino, Takayuki ^{[1
]}

Kandori, Shuya ^{[1
]}

Negoro, Hiromitsu ^{[1
]}

Kojima, Takahiro ^{[1
]}

Tanaka, Ryota ^{[3
]}

Okiyama, Naoko ^{[3
]}

Fujisawa, Yasuhiro ^{[3
]}

Watanabe, Miyuki ^{[4
]}

Yamasaki, Sho ^{[4
,5
,6
,7
]}

Kiyohara, Hideyasu ^{[8
]}

Watanabe, Makoto ^{[9
]}

Sato, Taka-aki ^{[9
]}

Tahara, Hideaki ^{[10
,11
]}

Nishiyama, Hiroyuki ^{[1
]}

Yano, Ikuya ^{[12
]}

机构：

[1] Univ Tsukuba, Fac Med, Dept Urol, Tsukuba, Ibaraki, Japan

[2] Int Univ Hlth & Welf, Sch Med, Dept Urol, 852 Hatakeda, Chiba 2860124, Japan

[3] Univ Tsukuba, Fac Med, Dept Dermatol, Tsukuba, Ibaraki, Japan

[4] Osaka Univ, Res Inst Microbial Dis, Dept Mol Immunol, Suita, Osaka, Japan

[5] Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Mol Immunol, Suita, Osaka, Japan

[6] Kyushu Univ, Med Inst Bioregulat, Div Mol Design, Higashi Ku, Fukuoka, Japan

[7] Chiba Univ, Med Mycol Res Ctr, Div Mol Immunol, Chuo Ku, Chiba, Japan

[8] Japan BCG Lab, Tokyo, Japan

[9] Life Sci Res Ctr, Technol Res Lab, Kyoto, Japan

[10] Univ Tokyo, Inst Med Sci, Project Div Canc Biomol Therapy, Tokyo, Japan

[11] Osaka Int Canc Ctr, Dept Canc Drug Discovery & Dev, Osaka, Japan

[12] Osaka City Univ, Osaka, Japan

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2021年 / 70卷 / 09期

基金：

日本学术振兴会;

关键词：

Trehalose dimycolate; Mincle; Antitumor immunity; Dendritic cell; BCG;

D O I：

10.1007/s00262-021-02870-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Intravesical Bovis bacillus Calmette-Guerin (BCG) therapy is the most effective immunotherapy for bladder cancer, but it sometime causes serious side effects because of its inclusion of live bacteria. It is necessary to develop a more active but less toxic immunotherapeutic agent. Trehalose 6,6 '-dimycolate (TDM), the most abundant hydrophobic glycolipid of the BCG cell wall, has been reported to show various immunostimulatory activities such as granulomagenesis and adjuvant activity. Here, we developed cationic liposomes incorporating TDM purified from Mycobacterium bovis BCG Connaught, and we investigated the antitumor effect of the cationic liposome TDM (Lip-TDM). Lip-TDM exerted an antitumor effect in bladder cancer, colon cancer, and melanoma-bearing mouse models that was comparable or even superior to that of BCG, with no body weight loss or granuloma formation. The antitumor effect of Lip-TDM disappeared in two types of mice: those with depletion of CD8(+) T cells, and those with knockout of macrophage-inducible C-type lectin (Mincle) which recognize TDM. Lip-TDM treatment enhanced the maturation and migration of dendritic cells in the tumor microenvironment in a Mincle-dependent manner. Our results elucidate mechanisms that underlie Lip-TDM treatment and suggest that Lip-TDM has potential as a safe and effective treatment for various cancers.

引用

页码：2529 / 2543

页数：15

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