Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1.
Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1.
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DOI：
10.1038/ni.2376
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发表时间：
2012-09
影响因子：
30.5
通讯作者：
Jinushi, Masahisa
中科院分区：
文献类型：
--
作者：
Chiba, Shigeki;Baghdadi, Muhammad;Akiba, Hisaya;Yoshiyama, Hironori;Kinoshita, Ichiro;Dosaka-Akita, Hirotoshi;Fujioka, Yoichiro;Ohba, Yusuke;Gorman, Jacob V.;Colgan, John D.;Hirashima, Mitsuomi;Uede, Toshimitsu;Takaoka, Akinori;Yagita, Hideo;Jinushi, Masahisa
肿瘤微环境调节核酸介导的先天免疫的机制仍然未知。在这里，我们确定受体TIM-3作为规避核酸在肿瘤免疫中的刺激作用的关键。小鼠肿瘤和癌症患者的肿瘤相关树突状细胞（DC）高表达TIM-3。DC衍生的TIM-3通过Toll样受体和胞质传感器经由半乳糖凝集素-9非依赖性机制识别核酸来抑制先天性免疫应答。相比之下，TIM-3与alarmin HMGB 1相互作用，干扰核酸募集到DC内体中，并通过降低从垂死肿瘤细胞释放的核酸的免疫原性来减弱DNA疫苗接种和化疗的治疗功效。我们的研究结果定义了肿瘤微环境抑制核酸介导的抗肿瘤免疫的机制。
The mechanisms by which tumor microenvironments modulate nucleic acid–mediated innate immunity remain unknown. Here we identify the receptor TIM-3 as key in circumventing the stimulatory effects of nucleic acids in tumor immunity. Tumor-associated dendritic cells (DCs) in mouse tumors and patients with cancer had high expression of TIM-3. DC-derived TIM-3 suppressed innate immune responses through the recognition of nucleic acids by Toll-like receptors and cytosolic sensors via a galectin-9-independent mechanism. In contrast, TIM-3 interacted with the alarmin HMGB1 to interfere with the recruitment of nucleic acids into DC endosomes and attenuated the therapeutic efficacy of DNA vaccination and chemotherapy by diminishing the immunogenicity of nucleic acids released from dying tumor cells. Our findings define a mechanism whereby tumor microenvironments suppress antitumor immunity mediated by nucleic acids.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
100.3
作者：
Kuchroo, Vijay K.;Dardalhon, Valerie;Anderson, Ana C.
通讯作者：
Anderson, Ana C.
DOI：
10.1084/jem.20081398
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jones RB;Ndhlovu LC;Barbour JD;Sheth PM;Jha AR;Long BR;Wong JC;Satkunarajah M;Schweneker M;Chapman JM;Gyenes G;Vali B;Hyrcza MD;Yue FY;Kovacs C;Sassi A;Loutfy M;Halpenny R;Persad D;Spotts G;Hecht FM;Chun TW;McCune JM;Kaul R;Rini JM;Nixon DF;Ostrowski MA
通讯作者：
Ostrowski MA
影响因子：
15.9
作者：
Besch, Robert;Poeck, Hendrik;Hartmann, Gunther
通讯作者：
Hartmann, Gunther
影响因子：
15.9
作者：
Drobits, Barbara;Holcmann, Martin;Sibilia, Maria
通讯作者：
Sibilia, Maria