| Title: | Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1 |
| Authors: | Chiba, Shigeki Browse this author |
| Baghdadi, Muhammad Browse this author |
| Akiba, Hisaya Browse this author |
| Yoshiyama, Hironori Browse this author →KAKEN DB |
| Kinoshita, Ichiro Browse this author →KAKEN DB |
| Dosaka-Akita, Hirotoshi Browse this author |
| Fujioka, Yoichiro Browse this author |
| Ohba, Yusuke Browse this author →KAKEN DB |
| Gorman, Jacob V. Browse this author |
| Colgan, John D. Browse this author |
| Hirashima, Mitsuomi Browse this author |
| Uede, Toshimitsu Browse this author →KAKEN DB |
| Takaoka, Akinori Browse this author →KAKEN DB |
| Yagita, Hideo Browse this author |
| Jinushi, Masahisa Browse this author |
| Keywords: | TIM-3 |
| HMGB1 |
| Nucleic acids |
| Innate immunity |
| Dendritic cells |
| Issue Date: | Sep-2012 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Nature Immunology |
| Volume: | 13 |
| Issue: | 9 |
| Start Page: | 832 |
| End Page: | 842 |
| Publisher DOI: | 10.1038/ni.2376 |
| Abstract: | The mechanisms by which tumor microenvironments modulate nucleic acid-mediated innate immunity remain unknown. Here, we identified the receptor TIM-3 as key to circumventing the stimulatory effects of nucleic acids in tumor immunity. TIM-3 is highly expressed on tumor-associated dendritic cells (DC) in murine tumors and cancer patients. DC-derived TIM-3 suppresses innate immune responses through Toll-like receptor and cytosolic sensor recognition of nucleic acids via a galectin-9 independent mechanism. Instead, TIM-3 interacts with the HMGB1 to interfere with recruitment of nucleic acids into DC endosomes and attenuates the therapeutic efficacy of DNA vaccination and chemotherapy by reducing immunogenicity of nucleic acids released from dying tumor cells. Together, these findings define a novel mechanism by which tumor microenvironments suppress antitumor immunity mediated by nucleic acids. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/52108 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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