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Proportions of blood-borne V?1+ and V?2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab.

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

SUBMITTER: Wistuba-Hamprecht K

PROVIDER: S-EPMC5201188 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Wistuba-Hamprecht Kilian K Martens Alexander A Haehnel Karin K Geukes Foppen Marnix M Yuan Jianda J Postow Michael A MA Wong Phillip P Romano Emanuela E Khammari Amir A Dreno Brigitte B Capone Mariaelena M Ascierto Paolo A PA Demuth Ilja I Steinhagen-Thiessen Elisabeth E Larbi Anis A Schilling Bastian B Schadendorf Dirk D Wolchok Jedd D JD Blank Christian U CU Pawelec Graham G Garbe Claus C Weide Benjamin B

European journal of cancer (Oxford, England : 1990) 20160709

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+ ce ...[more]

PMID: 27400322

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Project description:BACKGROUND:Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS:We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS:At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group. CONCLUSIONS:Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505 .).

Dataset Information

Proportions of blood-borne V?1+ and V?2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab.

Publications

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

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