The liposome of trehalose dimycolate extracted from M. bovis BCG induces antitumor immunity via the activation of dendritic cells and CD8+ T cells
The liposome of trehalose dimycolate extracted from M. bovis BCG induces antitumor immunity via the activation of dendritic cells and CD8+ T cells
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从牛分枝杆菌BCG中提取的海藻糖二霉菌酸酯脂质体通过激活树突状细胞和CD8 T细胞诱导抗肿瘤免疫
DOI：
10.1007/s00262-021-02870-2
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Tahara H
中科院分区：
文献类型：
--
作者：
Shiga Masanobu;Miyazaki Jun;Tanuma Kozaburo;Nagumo Yoshiyuki;Yoshino Takayuki;Kandori Shuya;Negoro Hiromitsu;Kojima Takahiro;Tanaka Ryota;Okiyama Naoko;Fujisawa Yasuhiro;Watanabe Miyuki;Yamasaki Sho;Kiyohara Hideyasu;Watanabe Makoto;Sato Taka-aki;Tahara H
膀胱灌注卡介苗（BCG）疗法是膀胱癌最有效的免疫疗法，但由于其包含活细菌，有时会导致严重的副作用。因此，有必要开发一种活性更强、毒性更低的免疫抑制剂。海藻糖6，6 ′-二霉菌酸酯（Trehalose 6，6 ′-dimycolate，TDM）是卡介苗细胞壁中最丰富的疏水性糖脂，具有多种免疫刺激活性，如肉芽肿形成和佐剂活性。本研究以牛分枝杆菌（MycobacteriumbovisBCG）康诺特为载体，制备了含TDM的阳离子脂质体，并对其抗肿瘤作用进行了研究。Lip-TDM在膀胱癌、结肠癌和荷黑色素瘤小鼠模型中发挥了与BCG相当甚至上级的抗肿瘤作用，没有体重减轻或肉芽肿形成。Lip-TDM的抗肿瘤作用在两种类型的小鼠中消失：CD 8 +T细胞耗竭的小鼠和识别TDM的巨噬细胞诱导的C型凝集素（Mincle）敲除的小鼠。Lip-TDM处理以Mincle依赖性方式增强肿瘤微环境中树突状细胞的成熟和迁移。我们的研究结果阐明了Lip-TDM治疗的机制，并表明Lip-TDM具有作为各种癌症的安全有效治疗的潜力。
IntravesicalBovis bacillusCalmette-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 fromMycobacterium bovisBCG 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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影响因子：
3.1
作者：
BEKIERKUNST, A;YARKONI, E
通讯作者：
YARKONI, E
硫脂 I 对海藻糖-6,6-二霉菌酸酯（索因子）毒性和抗肿瘤活性的影响
影响因子：
3.1
作者：
E. Yarkoni;M. Goren;H. Rapp
通讯作者：
H. Rapp
影响因子：
50.3
作者：
Roberts EW;Broz ML;Binnewies M;Headley MB;Nelson AE;Wolf DM;Kaisho T;Bogunovic D;Bhardwaj N;Krummel MF
通讯作者：
Krummel MF
合成 TDM 及其相关化合物对小鼠的致死毒性和佐剂活性。
影响因子：
5.5
作者：
T. Sakurai;I. Saiki;H. Ishida;K. Takeda*;I. Azuma
通讯作者：
I. Azuma
红色诺卡氏菌中碳水化合物部分不同的菌酰糖脂的平行抗肿瘤、肉芽肿形成和肿瘤坏死因子引发活性：结构-活性关系
DOI：
10.1007/bf01742373
发表时间：
2005
期刊：
Cancer Immunology, Immunotherapy
影响因子：
--
作者：
Y. Natsuhara;S. Oka;K. Kaneda;Y. Kato;I. Yano
通讯作者：
I. Yano