title: Tim-3 and its role in regulating anti-tumor immunity.
abstract: Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade. This has provided impetus to identify other co-inhibitory receptors that could be exploited to enhance response rates of current immunotherapeutic agents and achieve responses to the cancers that are refectory to immunotherapy. Tim-3 is a co-inhibitory receptor that is expressed on IFN-g-producing T cells, FoxP3+ Treg cells and innate immune cells (macrophages and dendritic cells) where it has been shown to suppress their responses upon interaction with their ligand(s). Tim-3 has gained prominence as a potential candidate for cancer immunotherapy, where it has been shown that in vivo blockade of Tim-3 with other check-point inhibitors enhances anti-tumor immunity and suppresses tumor growth in several preclinical tumor models. This review discusses the recent findings on Tim-3, the role it plays in regulating immune responses in different cell types and the rationale for targeting Tim-3 for effective cancer immunotherapy.
authors.affiliation: Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.|Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Das
authors.affiliation: Discovery Biology, Research and Development, Sanofi US, Cambridge, MA, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.|Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.|The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007109:Immunity; D056747:Immunomodulation; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019139:Tumor Escape
chemical_list: D000951:Antigens, Neoplasm; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D007371:Interferon-gamma
keywords: T cell exhaustion; Tim-3; checkpoint blockade; checkpoint inhibitors; immunotherapy; tumor immunity