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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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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
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)
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)

Submitter: 地主 将久

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