Phenotypic characterization and prognostic impact of circulating γδ and αβ T-cells in metastatic malignant melanoma

Abstract

Human T cells carrying γδ T-cell receptors (TCRs) represent a minor population relative to those with αβ TCRs. There has been much interest recently in the possibility of using these γδ T-cells in cancer therapy because they can kill tumor cells in vitro in an MHC-unrestricted manner, and possess potential regulatory capability and antigen-presenting capacity. The presence of γδ T-cells in late-stage melanoma patients and their relationship with survival has not been extensively explored, although relatively lower percentages of total γδ T-cells and Vδ2+ cells have been reported. Here, we present a detailed analysis of associations of γδ T-cell subsets and differentiation stages with survival in Stage IV patients, compared with CD4+ and CD8+ αβ T-cells. We found an increased Vδ1:Vδ2-ratio and a decreased CD4:CD8-ratio in patients compared to healthy controls, on the basis both of relative frequencies and absolute cell counts per μL blood. Nonetheless, Kaplan-Meier analyses showed that a higher than median frequency of Vδ1+ cells was negatively associated with survival, whereas there were no positive or negative associations with frequencies of Vδ2+ cells. Correlations of cell differentiation status with survival revealed a negative association of early-differentiated Vδ1+ T cells with survival, both on the basis of relative frequencies and absolute counts. There was also a positive correlation between the frequencies of early-differentiated CD8+ αβ T-cells and survival. Our findings suggest peripheral blood frequencies of Vδ1+ T-cells as a potential prognostic marker in melanoma. The mechanisms by which higher abundance of Vδ1+ cells are associated with poorer survival require determination. What's new? Human T cells carrying γδ receptors are able to kill tumor cells in vitro, and may be able to regulate the growth of cancer cells. Might levels of these or other T cells reflect the prognosis for particular cancers? In this study of stage IV melanoma patients, the authors found that patients with more circulating Vδ1+ T cells had lower survival rates, while patients with more circulating effector memory CD8+ αβ T-cells had improved survival. These findings suggest that the frequency Vδ1+ T-cells in peripheral blood may provide a useful prognostic biomarker in melanoma.