title: TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action.
abstract: Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy. Despite a large amount of experimental data showing an immune suppressive function of TIM-3 in vivo, the exact mechanisms are not well understood. To enable effective targeting of TIM-3 for tumor immunotherapy, further in-depth mechanistic studies are warranted. These studies will also provide much-needed insight for the rational design of novel combination therapy with other checkpoint blockers. In this review, we summarize key evidence supporting an immune regulatory role of TIM-3 and discuss possible mechanisms of action.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. daisy910917@163.com.|Department of Immunology, School of Medicine, University of Pittsburgh, EBST E1047, 200 Lothrop Street, Pittsburgh, PA 15261, USA. daisy910917@163.com.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Immunology, School of Medicine, University of Pittsburgh, EBST E1047, 200 Lothrop Street, Pittsburgh, PA 15261, USA. carolyangmin@163.com.|Department of Immunology, School of Biology and Basic Medical Science, Soochow University, Suzhou 215123, China. carolyangmin@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Immunology, School of Medicine, University of Pittsburgh, EBST E1047, 200 Lothrop Street, Pittsburgh, PA 15261, USA. alt126@pitt.edu.
authors.forename: Abbey
authors.initials: A
authors.lastname: Turner
authors.affiliation: Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130041, China. xucl@jlu.edu.cn.
authors.forename: Chunling
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Medicine, University of Pittsburgh, EBST E1047, 200 Lothrop Street, Pittsburgh, PA 15261, USA. ferrrl@upmc.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. huang_jian_an@163.com.
authors.forename: Jianan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Immunology, School of Medicine, University of Pittsburgh, EBST E1047, 200 Lothrop Street, Pittsburgh, PA 15261, USA. lkane@pitt.edu.
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Kane
authors.affiliation: Department of Immunology, School of Medicine, University of Pittsburgh, EBST E1047, 200 Lothrop Street, Pittsburgh, PA 15261, USA. binfeng@pitt.edu.
authors.forename: Binfeng
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D008024:Ligands; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008024:Ligands
keywords: T cell subsets; TIM-3; antitumor immune responses; tumor microenvironment