Targeting gamma delta T cells for cancer immunotherapy: bench to bedside

Indian J Med Res. 2013 Nov;138(5):755-61.

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.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Clinical Trials as Topic
  • Diphosphonates
  • Geranyltranstransferase
  • Hemiterpenes
  • Humans
  • Immunotherapy*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / immunology
  • Molecular Targeted Therapy*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocyte Subsets / immunology

Substances

  • Antibodies, Monoclonal
  • Diphosphonates
  • Hemiterpenes
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta
  • isopentenyl pyrophosphate
  • Interferon-gamma
  • Geranyltranstransferase