title: Taming dendritic cells with TIM-3: another immunosuppressive strategy used by tumors.
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.
authors.affiliation: Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jaina
authors.initials: J
authors.lastname: Patel
authors.forename: Erica N
authors.initials: EN
authors.lastname: Bozeman
authors.forename: Periasamy
authors.initials: P
authors.lastname: Selvaraj
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003713:Dendritic Cells / Q000276:immunology*; D024243:HMGB1 Protein / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D057131:Immune Evasion / Q000187:drug effects; D007108:Immune Tolerance; D007113:Immunity, Innate / Q000187:drug effects; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment
chemical_list: D000911:Antibodies, Monoclonal; C448908:HAVCR2 protein, human; D024243:HMGB1 Protein; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins