期刊
NATURE IMMUNOLOGY
卷 13, 期 9, 页码 832-842出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2376
关键词
-
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- National Cancer Center Research and Development Fund
- Institute for Genetic Medicine of Hokkaido University
- Takeda Science Foundation
- Sumitomo Foundation
- Terumo Life Science Foundation
- Senshin Medical Research Foundation
- Japan Leukemia Research Foundation
- Grants-in-Aid for Scientific Research [22591098, 23390090, 11J04616, 23659196, 21390113, 22240089, 22590360, 23590534, 23591132, 23501283] Funding Source: KAKEN
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据