title: Targeting gamma delta T cells for cancer immunotherapy: bench to bedside.
abstract: γδ T lymphocytes represent a minor subset of peripheral blood in humans (<10%). γδ T cells expressing Vγ9Vδ2 T cell receptor recognise the endogenous pool of isopentenyl pyrophosphate (IPP) that is overproduced in cancer cells as a result of dysregulated mevalonate pathway. Aminobisphosphonates increase the endogenous pool of IPP in cells by blocking the enzyme farnesyl pyrophosphate synthase (FPPS) of the mevalonate pathway. Activated γδ T cells release copious amounts of interferon (IFN)-γ and tumour necrosis factor (TNF)-α and exhibit potent anti-tumour activity. Combination of γδ T cells with therapeutic monoclonal antibodies can efficiently mediate antibody dependent cellular cytotoxicity against tumours. These features makes γδ T cells attractive mediator of cancer immunotherapy. We review here, the basic properties and importance of γδ T cells in tumour immunity, and highlight the key advances in anti-tumour effector functions of γδ T cells achieved over the last few years and also summarize the results of the clinical trials that have been done till date. Future immunotherapeutic approach utilizing γδ T cells holds considerable promise for treatment of different types of cancer.
authors.forename: Dimpu
authors.initials: D
authors.lastname: Gogoi
authors.affiliation: Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India.
authors.forename: Shubhada V
authors.initials: SV
authors.lastname: Chiplunkar
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004164:Diphosphonates; D051228:Geranyltranstransferase; D045782:Hemiterpenes; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D004164:Diphosphonates; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; C004809:isopentenyl pyrophosphate; D007371:Interferon-gamma; D051228:Geranyltranstransferase