Journal article
Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1
Nature immunology, Vol.13(9), pp.832-842
09/01/2012
DOI: 10.1038/ni.2376
PMCID: PMC3622453
PMID: 22842346
Abstract
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.
Details
- Title: Subtitle
- Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1
- Creators
- Shigeki Chiba - Hokkaido UniversityMuhammad Baghdadi - Hokkaido UniversityHisaya Akiba - Juntendo UniversityHironori Yoshiyama - Hokkaido UniversityIchiro Kinoshita - Hokkaido UniversityHirotoshi Dosaka-Akita - Hokkaido UniversityYoichiro Fujioka - Hokkaido UniversityYusuke Ohba - Hokkaido UniversityJacob V. Gorman - University of IowaJohn D. Colgan - University of IowaMitsuomi Hirashima - Kagawa UniversityToshimitsu Uede - Hokkaido UniversityAkinori Takaoka - Hokkaido UniversityHideo Yagita - Juntendo UniversityMasahisa Jinushi - Hokkaido University
- Resource Type
- Journal article
- Publication Details
- Nature immunology, Vol.13(9), pp.832-842
- Publisher
- Springer Nature
- DOI
- 10.1038/ni.2376
- PMID
- 22842346
- PMCID
- PMC3622453
- ISSN
- 1529-2908
- eISSN
- 1529-2916
- Number of pages
- 11
- Grant note
- Japan Leukemia Research Foundation Terumo Life Science Foundation Sumitomo Foundation Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) 11J04616 / Grants-in-Aid for Scientific Research; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research (KAKENHI) Takeda Science Foundation; Takeda Science Foundation (TSF) Institute for Genetic Medicine of Hokkaido University R01AI067489 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Senshin Medical Research Foundation; SENSHIN Medical Research Foundation National Cancer Center Research and Development Fund; National Cancer Center - Japan
- Language
- English
- Date published
- 09/01/2012
- Academic Unit
- Anatomy and Cell Biology; Immunology; Internal Medicine
- Record Identifier
- 9984284337302771
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