gammadelta T cells in cancer immunotherapy: current status and future prospects.
gammadelta T lymphocytes are a distinct T-cell subset that display unique features with respect to T-cell receptor (TCR) gene usage, tissue tropism and antigen recognition. Phosphoantigens contributed by a dysregulated mevalonate pathway or the bacterial nonmevalonate pathway and aminobisphosphonates are capable of activating Vgamma9Vdelta2 T cells. With the aid of synthetic phosphoantigens, large-scale expansion of gammadelta T cells and their adoptive transfer into human hosts is now possible. The present review summarizes triumphs and tribulations of clinical trials using gammadelta T-cell immunotherapy. Adoptive transfer of phosphoantigen-activated gammadelta T cells or coadministration with aminobisphosphonates/cytokines/monoclonal antibodies appear to be promising approaches for cancer immunotherapy. It can be predicted that a comprehensive understanding of the molecular interactions of this unique T-cell subset with other key immune regulators (dendritic cells and regulatory T cells) will provide an impetus to bring this modality of treatment from bench to bedside.
Chiplunkar
Shubhada
S
Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India. schiplunkar@actrec.gov.in
Dhar
Swati
S
Wesch
Daniela
D
Kabelitz
Dieter
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002450:Cell Communication; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology*; D004338:Drug Combinations; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000639:trends*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D004338:Drug Combinations; D016692:Receptors, Antigen, T-Cell, gamma-delta