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

Human T cells carrying gamma delta T-cell receptors (TCRs) represent a minor population relative to those with alpha beta TCRs. There has been much interest recently in the possibility of using these gamma delta 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 gamma delta T-cells in late-stage melanoma patients and their relationship with survival has not been extensively explored, although relatively lower percentages of total gamma delta T-cells and V delta 2+ cells have been reported. Here, we present a detailed analysis of associations of gamma delta T-cell subsets and differentiation stages with survival in Stage IV patients, compared with CD4+ and CD8+ alpha beta T-cells. We found an increased V delta 1:V delta 2-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 mu L blood. Nonetheless, Kaplan-Meier analyses showed that a higher than median frequency of V delta 1+ cells was negatively associated with survival, whereas there were no positive or negative associations with frequencies of V delta 2+ cells. Correlations of cell differentiation status with survival revealed a negative association of early-differentiated V delta 1+ 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+ alpha beta T-cells and survival. Our findings suggest peripheral blood frequencies of V delta 1+ T-cells as a potential prognostic marker in melanoma. The mechanisms by which higher abundance of V delta 1+ cells are associated with poorer survival require determination.