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

Human gamma delta T-cells possess regulatory and cytotoxic capabilities, and could potentially influence the efficacy of immunotherapies. We analysed the frequencies of peripheral gd T-cells, including their most prominent subsets (V delta 1+ and V delta 2+ cells) and differentiation states in 109 melanoma patients and 109 healthy controls. We additionally analysed the impact of gamma delta T-cells on overall survival (OS) calculated from the first dose of ipilimumab in melanoma patients. Higher median frequencies of V delta 1+ cells and lower median frequencies of V delta 2+ cells were identified in patients compared to healthy subjects (V delta 1+: 30% versus 15%, V delta 2+: 39% versus 64%, both p < 0.001). Patients with higher frequencies of V delta 1+ cells (>= 30%) had poorer OS (p = 0.043) and a V delta 1+ differentiation signature dominated by late-differentiated phenotypes. In contrast, higher frequencies of V delta 2+ cells (>= 39%) were associated with longer survival (p = 0.031) independent of the M category or lactate dehydrogenase level. Patients with decreasing frequencies of V delta 2+ 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 V delta 1+ and V delta 2+ 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 gamma delta T-cells are specifically and/or functionally linked to the mode of action of ipilimumab. (C) 2016 Elsevier Ltd. All rights reserved.