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Published on: June 22, 2016
Phenotypic and functional alterations of Vgamma2Vdelta2 T cell subsets in patients with active nasopharyngeal
Kia Joo Puan1, John Seng Hooi Low, Terence Wee Kiat Tan
1Bek 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
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.
Insights
Vgamma2Vdelta2 T cells in nasopharyngeal carcinoma (NPC) patients show reduced tumor cell cytotoxicity due to altered subsets and impaired cytokine production. These changes, exacerbated by treatment, highlight compromised gammadelta T cell function in NPC.
Area of Science:
- Immunology
- Oncology
Background:
- Human Vgamma2Vdelta2 T cells are crucial for immunity, recognizing isoprenoid metabolites via gammadelta T cell receptors.
- These T cells, similar to other T cell types, exhibit heterogeneity in function within adult peripheral blood.
Purpose of the Study:
- To characterize Vgamma2Vdelta2 T cell phenotypes and functions in nasopharyngeal carcinoma (NPC) patients.
- To understand the role of these cells in NPC pathogenesis and inform immunotherapeutic strategies.
Main Methods:
- Comparative analysis of Vgamma2Vdelta2 T cell subsets from 96 NPC patients and 54 healthy controls.
- Phenotypic characterization and assessment of cytokine production (IFN-gamma, TNF-alpha) and cytotoxicity against tumor cells.
Main Results:
- NPC patients and healthy donors had similar total Vgamma2Vdelta2 T cell percentages, but NPC patients exhibited decreased cytotoxicity.
- NPC patients showed increased late effector memory (T(EM RA)) and decreased early memory (T(CM)) Vgamma2Vdelta2 T cells.
- Impaired IFN-gamma and TNF-alpha production was observed in T(EM RA) and T(CM) cells from NPC patients, correlating with reduced cytotoxicity.
Conclusions:
- Distinct alterations in Vgamma2Vdelta2 T cell subsets are present in NPC patients, leading to compromised gammadelta T cell effector function.
- The effectiveness of Vgamma2Vdelta2 T cells in controlling NPC may be dependent on their activation state and differentiation.
- Radiotherapy or chemo-radiotherapy in NPC patients increased T(EM RA) cells but did not restore impaired cytokine production.
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