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Phenotypic and functional alterations of Vγ2Vδ2 T cell subsets in patients with active nasopharyngeal carcinoma

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Abstract

Introduction

Human Vγ2Vδ2 T cells play important role in immunity to infection and cancer by monitoring self and foreign isoprenoid metabolites with their γδ T cell antigen receptors. Like CD4 and CD8 αβ T cells, adult peripheral Vγ2Vδ2 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 Vγ2Vδ2 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 Vγ2Vδ2 T cells were found in both NPC patients and normal donors, Vγ2Vδ2 T cells from NPC patients showed decreased cytotoxicity against tumor cells whereas Vγ2Vδ2 T cells from normal donors showed potent cytotoxicity. To investigate further, we compared the phenotypic characteristics of Vγ2Vδ2 T cells from 96 patients with NPC and 54 healthy controls. The fraction of late effector memory Vγ2Vδ2 T cells (TEM RA) was significantly increased in NPC patients with corresponding decreases in the fraction of early memory Vγ2Vδ2 T cells (TCM) compared with those in healthy controls. Moreover, TEM RA and TCM Vγ2Vδ2 cells from NPC patients produced significantly less IFN-γ and TNF-α, potentially contributing to their impaired cytotoxicity. Radiotherapy or concurrent chemo-radiotherapy further increased the TEM RA Vγ2Vδ2 T cell population but did not correct the impaired production of IFN-γ and TNF-α observed for TEM RA Vγ2Vδ2 T cells.

Conclusion

We have identified distinct alterations in the Vγ2Vδ2 T cell subsets of patients with NPC. Moreover, the overall cellular effector function of γδ T cells is compromised in these patients. Our data suggest that the contribution of Vγ2Vδ2 T cells to control NPC may depend on the activation state and differentiation of these cells.

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Abbreviations

HMBPP:

(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate

IPP:

Isopentenyl pyrophosphate

NOR:

Healthy controls

NPC:

Nasopharyngeal carcinoma

SCC:

Non-keratinizing squamous cell carcinoma

TCR:

T cell antigen receptor

TCM :

CD28+ CD27+ central memory T

TCM 27− :

CD28+ CD27 central memory T

TEM :

CD28 CD27+ effector memory T

TEM RA :

CD28 CD27 CD45RA+ effector memory T

UNC:

Undifferentiated carcinoma

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Acknowledgments

We thank Florencia Goh, Jolin Ning Ning, and Lan Yin Wang of the Division of Clinical Trials and Epidemiological Sciences, National Cancer Center, for their efforts in collecting the blood samples and the patients’ clinical data. This work was supported by the Biomedical Research Council of Singapore, National Medical Research Council of Singapore, Singapore Millennium Foundation Fund to K.M.H.; a Singapore Millennium Foundation Scholarship to K.J.P.; and the NIH National Institute of Arthritis and Musculoskeletal and Skin Disease (AR45504), the National Institute of Allergy and Infectious Diseases (Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, AI057160), and the National Cancer Institute (CA113874) to C.T.M.

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None of the authors has a financial or other relationship that might lead to a conflict of interest.

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Correspondence to Kam M. Hui.

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Puan, K.J., Low, J.S.H., Tan, T.W.K. et al. Phenotypic and functional alterations of Vγ2Vδ2 T cell subsets in patients with active nasopharyngeal carcinoma. Cancer Immunol Immunother 58, 1095–1107 (2009). https://doi.org/10.1007/s00262-008-0629-8

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