Phenotypic and Functional Alterations of Vγ2Vδ2 T Cell Subsets in Patients with Active Nasopharyngeal Carcinoma

Kia Joo Puan; John Seng Hooi Low; Terence Wee Kiat Tan; Joseph Tien Seng Wee; Eng Huat Tan; Kam Weng Fong; Eu Tiong Chua; Chenggang Jin; José-Luis Giner; Craig T Morita; Christopher Hood Keng Goh; Kam M Hui

doi:10.1007/s00262-008-0629-8

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Phenotypic and Functional Alterations of Vγ2Vδ2 T Cell Subsets in Patients with Active Nasopharyngeal Carcinoma

Journal article

Peer reviewed

Phenotypic and Functional Alterations of Vγ2Vδ2 T Cell Subsets in Patients with Active Nasopharyngeal Carcinoma

Kia Joo Puan, John Seng Hooi Low, Terence Wee Kiat Tan, Joseph Tien Seng Wee, Eng Huat Tan, Kam Weng Fong, Eu Tiong Chua, Chenggang Jin, José-Luis Giner, Craig T Morita, …

Cancer immunology, immunotherapy : CII, Vol.58(7), pp.1095-1107

07/2009

DOI: 10.1007/s00262-008-0629-8

PMCID: PMC2695875

PMID: 19043708

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Abstract

Introduction: 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. Purpose: 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. Conclusion: 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.

Nasopharyngeal carcinoma

IFN-γ

TNF-α

Peripheral Vγ2Vδ2 T cells

CD28

CD27

Memory Vγ2Vδ2 T cell subsets

Details

Title: Subtitle: Phenotypic and Functional Alterations of Vγ2Vδ2 T Cell Subsets in Patients with Active Nasopharyngeal Carcinoma
Creators: Kia Joo Puan - Bek Chai Heah Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore
John Seng Hooi Low - Department of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive Singapore 169610, Singapore
Terence Wee Kiat Tan - Department of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive Singapore 169610, Singapore
Joseph Tien Seng Wee - Department of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive Singapore 169610, Singapore
Eng Huat Tan - Department of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive Singapore 169610, Singapore
Kam Weng Fong - Department of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive Singapore 169610, Singapore
Eu Tiong Chua - Department of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive Singapore 169610, Singapore
Chenggang Jin - Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, EMRB 400F, Iowa City, IA 52242, USA
José-Luis Giner - Department of Chemistry, State University of New York-ESF, Syracuse, NY 13210, USA
Craig T Morita - Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, EMRB 400F, Iowa City, IA 52242, USA
Christopher Hood Keng Goh - Department of Otolaryngology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore
Kam M Hui - Bek Chai Heah Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore
Resource Type: Journal article
Publication Details: Cancer immunology, immunotherapy : CII, Vol.58(7), pp.1095-1107
DOI: 10.1007/s00262-008-0629-8
PMID: 19043708
PMCID: PMC2695875
NLM abbreviation: Cancer Immunol Immunother
ISSN: 0340-7004
eISSN: 1432-0851
Publisher: Springer Science and Business Media LLC
Language: English
Date published: 07/2009
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094743902771

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