Taming dendritic cells with TIM-3: Another immunosuppressive strategy by tumors

• Type of Material: Article
• Authors: Jaina Patel, Emory University; Erica Bozeman, Emory University; Periasamy Selvaraj, Emory University
• Language: English
• Date: 2012-12
• Publisher: Future Medicine
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Future Medicine © 2014
• Final Published Version (URL): http://www.futuremedicine.com/doi/abs/10.2217/imt.12.126?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
• Title of Journal or Parent Work: Immunotherapy
• ISSN: 1750-743X
• Volume: 4
• Issue: 12
• Start Page: 1795
• End Page: 1798
• Grant/Funding Information: This work was supported by NIH grants 1 R01 CA138993-01A1 (PS), 1 F31 CA165632-01 (JMP) and 1 F31 CA165897-01 (EB).
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology

Abstract

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 mAb treated mice or mice depleted of all DCs which indicated that significant role played by TADCs 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.