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：0
作者：
Masanobu Shiga
Jun Miyazaki
Kozaburo Tanuma
Yoshiyuki Nagumo
Takayuki Yoshino
Shuya Kandori
Hiromitsu Negoro
Takahiro Kojima
Ryota Tanaka
Naoko Okiyama
Yasuhiro Fujisawa
Miyuki Watanabe
Sho Yamasaki
Hideyasu Kiyohara
Makoto Watanabe
Taka-aki Sato
Hideaki Tahara
Hiroyuki Nishiyama
Ikuya Yano
机构：
[1] University of Tsukuba,Department of Urology, Faculty of Medicine
[2] International University of Health and Welfare,Department of Urology, School of Medicine
[3] University of Tsukuba,Department of Dermatology, Faculty of Medicine
[4] Research Institute for Microbial Diseases,Department of Molecular Immunology
[5] Osaka University,Laboratory of Molecular Immunology, Immunology Frontier Research Center (WPI
[6] Osaka University,IFReC)
[7] Kyushu University,Division of Molecular Design, Medical Institute of Bioregulation
[8] Chiba University,Division of Molecular Immunology, Medical Mycology Research Center
[9] Japan BCG Laboratory,Life Science Research Center, Technology Research Laboratory
[10] Shimadzu,Project Division of Cancer Biomolecular Therapy
[11] The Institute of Medical Science,Department of Cancer Drug Discovery and Development
[12] The University of Tokyo,undefined
[13] Osaka International Cancer Center,undefined
[14] Osaka City University,undefined
来源：
Cancer Immunology, Immunotherapy | 2021年 / 70卷
关键词：
Trehalose dimycolate; Mincle; Antitumor immunity; Dendritic cell; BCG;
D O I：
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学科分类号：
摘要：
Intravesical Bovis bacillus Calmette-Guérin (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.
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页码：2529 / 2543
页数：14
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