title: Tim-3 and Tim-4 as the potential targets for antitumor therapy.
abstract: Both Tim-3 and Tim-4 belong to the T-cell immunoglobulin and mucin domain (Tim) gene family, which plays a critical role in immunoregulation. Tim-3 has been suggested as a negative regulator of anti-tumor immunity due to its function on inducing T cells exhaustion in cancer. In addition to its expression on exhausted T cells, Tim-3 also has been reported to up-regulate on nature killer (NK) cells and promote NK cells functionally exhausted in cancer. While Tim-3 selectively expression on most types of leukemia stem cells, it promotes the progression of acute myeloid leukemia. Recently, data from experimental models of tumor discovered that Tim-3 and Tim-4 up-regulation on tumor associated dendritic cells and macrophages attenuated the anti-tumor effects of cancer vaccines and chemotherapy. Moreover, co-blockage of Tim-3 and PD-1, Tim-3 and CD137, Tim-3 and carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) could enhance cell-mediated immunity in advanced tumor, and combined treatment with anti-Tim-3 and anti-Tim-4 mAbs further increase the efficacy of cancer vaccines. The therapeutic manipulation of TIM-3 and TIM-4 may provide a novel strategy to improve the clinical efficacy of cancer immunotherapy.
authors.affiliation: a Institute of Burn Research; Southwest Hospital; Third Military Medical University ; Chongqing , China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: b Department of Oncology; Southwest Hospital ; Third Military Medical University ; Chongqing , China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ruan
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D023421:Models, Animal; D008962:Models, Theoretical; D009369:Neoplasms / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; C512411:TIMD4 protein, human
keywords: Tim-3; Tim-4; chemotherapy; immunotherapy; tumor immunity