Proportions of blood-borne Vδ1+ and Vδ2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab

• Published in: European journal of cancer (1990) Vol. 64; pp. 116 - 126
• Main Authors: Wistuba-Hamprecht, Kilian, Martens, Alexander, Haehnel, Karin, Geukes Foppen, Marnix, Yuan, Jianda, Postow, Michael A., Wong, Phillip, Romano, Emanuela, Khammari, Amir, Dreno, Brigitte, Capone, Mariaelena, Ascierto, Paolo A., Demuth, Ilja, Steinhagen-Thiessen, Elisabeth, Larbi, Anis, Schilling, Bastian, Schadendorf, Dirk, Wolchok, Jedd D., Blank, Christian U., Pawelec, Graham, Garbe, Claus, Weide, Benjamin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2016
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - therapeutic use; Biomarker; Biomarkers, Tumor - blood; Case-Control Studies; Cell Differentiation; Female; Flow Cytometry; Hematology, Oncology and Palliative Medicine; Humans; Immunotherapy; Immunotherapy - methods; Ipilimumab; Male; Melanoma; Melanoma - drug therapy; Melanoma - immunology; Middle Aged; Prognosis; Receptors, Antigen, T-Cell, gamma-delta - blood; Survival; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; γδ T-cells; Biomarker; Survival; Ipilimumab; Immunotherapy; Melanoma; γδ T-cells
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2016.06.001

Human γδ T-cells possess regulatory and cytotoxic capabilities, and could potentially influence the efficacy of immunotherapies. We analysed the frequencies of peripheral γδ T-cells, including their most prominent subsets (Vδ1+ and Vδ2+ cells) and differentiation states in 109 melanoma patients and 109 healthy controls. We additionally analysed the impact of γδ T-cells on overall survival (OS) calculated from the first dose of ipilimumab in melanoma patients. Higher median frequencies of Vδ1+ cells and lower median frequencies of Vδ2+ cells were identified in patients compared to healthy subjects (Vδ1+: 30% versus 15%, Vδ2+: 39% versus 64%, both p < 0.001). Patients with higher frequencies of Vδ1+ cells (≥30%) had poorer OS (p = 0.043) and a Vδ1+ differentiation signature dominated by late-differentiated phenotypes. In contrast, higher frequencies of Vδ2+ cells (≥39%) were associated with longer survival (p = 0.031) independent of the M category or lactate dehydrogenase level. Patients with decreasing frequencies of Vδ2+ cells under ipilimumab treatment had worse OS and a lower rate of clinical benefit than patients without such decreases. Therefore, we suggest frequencies of both Vδ1+ and Vδ2+ cells as candidate biomarkers for outcome in melanoma patients following ipilimumab. Further studies are needed to validate these results and to clarify whether they represent prognostic associations or whether γδ T-cells are specifically and/or functionally linked to the mode of action of ipilimumab. •Frequencies of γδ T-cells are different in melanoma patients and controls.•Higher Vδ2+ and lower Vδ1+ T-cell levels in blood are prognostic for survival.•Decreasing Vδ2 cells during ipilimumab treatment is associated with poorer survival.