title: The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy.
abstract: γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of human γδ T cell receptors (TCRs) remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδ T cell compartment in cancer immunosurveillance and paving the way for the use of γδ TCRs in cancer therapy. Ligand recognition by the γδ TCR often requires accessory/co-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδ T cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment.
authors: Division of Infection and Immunity and Systems Immunity University Research Institute, Cardiff University School of Medicine, Cardiff, UK.
authors: Mateusz
authors: M
authors: Legut
authors: Division of Infection and Immunity and Systems Immunity University Research Institute, Cardiff University School of Medicine, Cardiff, UK.
authors: David K
authors: DK
authors: Cole
authors: Division of Infection and Immunity and Systems Immunity University Research Institute, Cardiff University School of Medicine, Cardiff, UK.
authors: Andrew K
authors: AK
authors: Sewell
mesh_terms: D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D002986:Clinical Trials as Topic; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D045782:Hemiterpenes / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008024:Ligands; D008958:Models, Molecular; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009943:Organophosphorus Compounds / Q000276:immunology; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
chemical_list: D018949:Antigens, CD1; D000951:Antigens, Neoplasm; D045782:Hemiterpenes; D008024:Ligands; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; C004809:isopentenyl pyrophosphate