Dataset Information

Phenotypic and functional alterations of Vgamma2Vdelta2 T cell subsets in patients with active nasopharyngeal carcinoma.

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.

SUBMITTER: Puan KJ

PROVIDER: S-EPMC2695875 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Publications

Phenotypic and functional alterations of Vgamma2Vdelta2 T cell subsets in patients with active nasopharyngeal carcinoma.

Puan Kia Joo KJ Low John Seng Hooi JS Tan Terence Wee Kiat TW Wee Joseph Tien Seng JT Tan Eng Huat EH Fong Kam Weng KW Chua Eu Tiong ET Jin Chenggang C Giner José-Luis JL Morita Craig T CT Goh Christopher Hood Keng CH Hui Kam M KM

Cancer immunology, immunotherapy : CII 20081130 7

<h4>Introduction</h4>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.<h4>Purpose</h4>The aim of this study was to characterize the phenotypes and functions of various Vgamma2Vdelta2 T cell subsets in patient ...[more]

PMID: 19043708

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Project description:Background and purposeTo investigate effects of radiotherapy on normal brain tissue using in vivo neuroimaging in patients with nasopharyngeal carcinoma (NPC).Methods and materialsWe used longitudinal MRI to monitor structural brain changes during standard radiotherapy in patients newly diagnosed with NPC. We assessed volumetric measures in 63 patients at 2-3 time points before and after radiotherapy, with 20 NPC-free participants as normal controls. Images were processed using validated software (FreeSurfer). Automated results were inspected visually for accuracy. We examined changes in volume of the whole brain, gray matter, white matter, and ventricles, as well as in cerebral volumes partitioned into temporal, frontal, parietal, and occipital lobes. A linear mixed model was used to evaluate longitudinal changes in these measurements. Statistical significance was evaluated at p < 0.05, which was corrected for multiple comparisons.ResultsVolumes of the gray matter, and bilateral temporal lobes decreased in a time-dependent manner, whereas ventricle volume showed a time-dependent increase after radiotherapy. No volume changes were detected in NPC patients before radiotherapy when compared normal controls. No volume changes were detected in the subcohort of patients after completion of induction chemotherapy but prior to initiation of radiotherapy. Changes of bilateral temporal lobe volume correlated with irradiation dose in this region. Expansion of the ventricles correlated with a reduction in cognition assessment.ConclusionsWe detected significant and progressive radiotherapy-associated structural changes in the brains of patients with NPC who were treated with standard radiotherapy, especially in the bilateral temporal lobe in which the effect was dose-dependent. Expansion of the ventricles can serve as an imaging marker for treatment-related reduction in cognitive function. Future studies with longer follow-ups are needed to evaluate morphometric changes long-term after radiotherapy.

Project description:BackgroundChemoradiotherapy (CRT) is the primary and most effective treatment for non-metastatic nasopharyngeal carcinoma (NPC), exerting antitumor effects by modulating immune cells. Distinct subpopulations of immune cells exhibit specific sensitivity to CRT. This study aimed to characterize the dynamics of the proportions and absolute counts of peripheral circulating lymphocyte subsets in non-metastatic NPC before and after CRT, and to elucidate their association with clinical responses.MethodsA total of 91 patients with non-metastatic NPC were enrolled. Flow cytometry was employed to detect the expression of CD3, CD4, CD8, CD56, and CD19 on peripheral blood cells. The composition of lymphocyte subsets before treatment, post-completion of CRT, and one month following CRT was retrospectively analyzed. Further, the relationship between the composition of circulating lymphocyte subpopulations and distinguish clinical responses was evaluated.ResultsThe proportion of CD3+ T cells showed an initial increase followed by a significant decrease at baseline, post-completion of CRT, and one month following CRT. The proportions of CD3+CD4+ T cells, CD4+/CD8+ ratio, and CD19+ B cells continued to decline at baseline, post-completion of CRT, and one month following CRT, while the proportions of CD3+CD8+ T cells and CD16+CD56+ NK cells progressively increased. The absolute counts of circulating lymphocyte subsets, including CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, CD45+, CD19+ B cells, and CD16+CD56+ NK cells, demonstrated a trend of initial decrease followed by an increase at baseline, post-completion of CRT, and one month following CRT. Patients with complete response (CR) and partial response (PR) presented similar dynamic trends in the percentages and absolute counts of circulating lymphocyte subpopulations at baseline, post-completion of CRT, and one month following CRT. The proportions and absolute counts of CD3+CD4+ T cells in CR patients were distinctly higher than those in PR patients at the end of CRT, whereas the absolute counts of CD16+CD56+ NK cells were remarkably lower in CR patients compared to PR patients. The baseline proportion and absolute count of CD19+ B cells, as well as the absolute count of CD3+CD4+ T cells, were significantly higher in CR patients compared with PR patients.ConclusionCRT induced dynamic alterations in the peripheral lymphocyte profile of non-metastatic NPC patients. Assessing the variations in the distribution of circulating lymphocyte subsets among patients with different clinical treatment responses will be helpful in developing protocols for the concurrent utilization of immunotherapeutic drugs and CRT.

Dataset Information

Phenotypic and functional alterations of Vgamma2Vdelta2 T cell subsets in patients with active nasopharyngeal carcinoma.

Introduction

Purpose

Results

Conclusion

Publications

Phenotypic and functional alterations of Vgamma2Vdelta2 T cell subsets in patients with active nasopharyngeal carcinoma.

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