title: TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy.
abstract: While therapies targeting the co-inhibitory or immune checkpoint receptors PD-1 and CTLA-4 have shown remarkable success in many cancers, not all patients benefit from these therapies. This has catalyzed enormous interest in the targeting of other immune checkpoint receptors. In this regard, TIGIT and CD96 have recently entered the limelight as novel immune checkpoint receptor targets. TIGIT and CD96 together with the co-stimulatory receptor CD226 form a pathway that is analogous to the CD28/CTLA-4 pathway, in which shared ligands and differential receptor:ligand affinities fine-tune the immune response. Although the roles of TIGIT and CD96 as immune checkpoint receptors in T cell and natural killer cell biology are just beginning to be uncovered, accumulating data support the targeting of these receptors for improving anti-tumor immune responses. A clear understanding of the immune cell populations regulated by TIGIT and CD96 is key to the design of immunotherapies that target these receptors in combination with other existing immune checkpoint blockade therapies.
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: William C
authors.initials: WC
authors.lastname: Dougall
authors.affiliation: Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Sema
authors.initials: S
authors.lastname: Kurtulus
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.|School of Medicine, The University of Queensland, Herston, QLD, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.affiliation: Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; C116131:CD96 antigen; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; C534712:TIGIT protein, human
keywords: 
  TIGIT
  ; CD96; anti-tumor immunity; cancer immunotherapy; checkpoint inhibitors; co-inhibitory receptors