Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1

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

Title	en Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1
Creator	en Chiba, Shigeki en Baghdadi, Muhammad en Akiba, Hisaya en Yoshiyama, Hironori NRID 1000010253147 en Kinoshita, Ichiro NRID 1000040343008 en Dosaka-Akita, Hirotoshi en Fujioka, Yoichiro en Ohba, Yusuke NRID 1000030333503 en Gorman, Jacob V. en Colgan, John D. en Hirashima, Mitsuomi en Uede, Toshimitsu NRID 1000000160185 en Takaoka, Akinori NRID 1000030323611 en Yagita, Hideo en Jinushi, Masahisa
Accessrights	open access
Subject	Other en TIM-3 Other en HMGB1 Other en Nucleic acids Other en Innate immunity Other en Dendritic cells NDC 493
Description	Abstract en 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.
Publisher	en Nature Publishing Group
Date	Issued2012-09
Language	eng
Resource Type	journal article
Version Type	AM
Identifier	HDL http://hdl.handle.net/2115/52108
Relation	isVersionOf DOI https://doi.org/10.1038/ni.2376
Journal	PISSN 1529-2908 en Nature Immunology Volume Number13 Issue Number9 Page Start832 Page End842
File	fulltext NI13-9_832-842.pdf 2.88 MB (application/pdf) Issued2012-09 fulltext Supplementary_information.pdf 718.05 KB (application/pdf) Issued2012-09
Oaidate	2023-07-26