title: Phenotypic and functional alterations of Vgamma2Vdelta2 T cell subsets in patients with active nasopharyngeal carcinoma.
abstract: BACKGROUND
  Human Vgamma2Vdelta2 T cells play important role in immunity to infection and cancer by monitoring self and foreign isoprenoid metabolites with their gammadelta T cell antigen receptors. Like CD4 and CD8 alphabeta T cells, adult peripheral Vgamma2Vdelta2 T cells represent a pool of heterogeneous cells with distinct functional capabilities.
  
  
  OBJECTIVE
  The aim of this study was to characterize the phenotypes and functions of various Vgamma2Vdelta2 T cell subsets in patients with nasopharyngeal carcinoma (NPC). We sought to develop a better understanding of the role of these cells during the course of disease and to facilitate the development of immunotherapeutic strategies against NPC.
  
  
  RESULTS
  Although similar total percentages of peripheral blood Vgamma2Vdelta2 T cells were found in both NPC patients and normal donors, Vgamma2Vdelta2 T cells from NPC patients showed decreased cytotoxicity against tumor cells whereas Vgamma2Vdelta2 T cells from normal donors showed potent cytotoxicity. To investigate further, we compared the phenotypic characteristics of Vgamma2Vdelta2 T cells from 96 patients with NPC and 54 healthy controls. The fraction of late effector memory Vgamma2Vdelta2 T cells (T(EM RA)) was significantly increased in NPC patients with corresponding decreases in the fraction of early memory Vgamma2Vdelta2 T cells (T(CM)) compared with those in healthy controls. Moreover, T(EM RA) and T(CM) Vgamma2Vdelta2 cells from NPC patients produced significantly less IFN-gamma and TNF-alpha, potentially contributing to their impaired cytotoxicity. Radiotherapy or concurrent chemo-radiotherapy further increased the T(EM RA) Vgamma2Vdelta2 T cell population but did not correct the impaired production of IFN-gamma and TNF-alpha observed for T(EM RA) Vgamma2Vdelta2 T cells.
  
  
  CONCLUSIONS
  We have identified distinct alterations in the Vgamma2Vdelta2 T cell subsets of patients with NPC. Moreover, the overall cellular effector function of gammadelta T cells is compromised in these patients. Our data suggest that the contribution of Vgamma2Vdelta2 T cells to control NPC may depend on the activation state and differentiation of these cells.
authors.affiliation: Bek Chai Heah Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore. ncmpkj@nccs.com.sg
authors.forename: Kia Joo
authors.initials: KJ
authors.lastname: Puan
authors.forename: John Seng Hooi
authors.initials: JS
authors.lastname: Low
authors.forename: Terence Wee Kiat
authors.initials: TW
authors.lastname: Tan
authors.forename: Joseph Tien Seng
authors.initials: JT
authors.lastname: Wee
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.forename: Kam Weng
authors.initials: KW
authors.lastname: Fong
authors.forename: Eu Tiong
authors.initials: ET
authors.lastname: Chua
authors.forename: Chenggang
authors.initials: C
authors.lastname: Jin
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Giner
authors.forename: Craig T
authors.initials: CT
authors.lastname: Morita
authors.forename: Christopher Hood Keng
authors.initials: CH
authors.lastname: Goh
authors.forename: Kam M
authors.initials: KM
authors.lastname: Hui
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000276:immunology* / Q000532:radiotherapy; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000532:radiotherapy; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma