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Immunotherapy. 2012 Dec;4(12):1795-8. doi: 10.2217/imt.12.126.

Taming dendritic cells with TIM-3: another immunosuppressive strategy used by tumors.

Author information

1
Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Abstract

Evaluation of: Chiba S, Baghdadi M, Akiba H et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat. Immunol. 13, 832-842 (2012). The identification of TIM-3 expression on tumor-associated dendritic cells (TADCs) provides insight into another aspect of tumor-mediated immunosuppression. The role of TIM-3 has been well characterized on tumor-infiltrating T cells; however, its role on TADCs was not previously known. The current paper demonstrated that TIM-3 was predominantly expressed by TADCs and its interaction with the nuclear protein HMGB1 suppressed nucleic acid-mediated activation of an effective antitumor immune response. The authors were able to show that TIM-3 interaction with HMGB1 prevented the localization of nucleic acids into endosomal vesicles. Furthermore, chemotherapy was found to be more effective in anti-TIM-3 monoclonal antibody-treated mice or mice depleted of all DCs, which indicated that a significant role is played by TADCs in inhibiting tumor regression. Taken together, these findings identify TIM-3 as a potential target for inducing antitumor immunity in conjunction with DNA vaccines and/or immunogenic chemotherapy in clinical settings.

PMID:
23240746
PMCID:
PMC4020625
DOI:
10.2217/imt.12.126
[Indexed for MEDLINE]
Free PMC Article

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