title: 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.
authors.affiliation: Department of Internal Medicine II, University Medical Center, Tübingen, Germany.|Department of Dermatology, University Medical Center, Tübingen, Germany.
authors.forename: Kilian
authors.initials: K
authors.lastname: Wistuba-Hamprecht
authors.affiliation: Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Di Benedetto
authors.affiliation: Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schilling
authors.affiliation: Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Sucker
authors.affiliation: Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany.|Department of Immunology, University of Tübingen, Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weide
authors.affiliation: Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
mesh_terms: D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: biomarker; malignant melanoma; survival; γδ T-cells