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Proportions of blood-borne Vd1þ and Vd2þ T-cells are associated with overall survival of melanoma patients treated with ipilimumab

Kilian Wistuba-Hamprecht 1, 2, * Alexander Martens 1, 2 Karin Haehnel 2 Marnix Geukes Foppen 3 Jianda Yuan 4 Michael Postow 5, 4 Phillip Wong 4 Emanuela Romano 6 Amir Khammari 7, 8 Brigitte Dreno 7, 8 Mariaelena Capone 9 Paolo Ascierto 9 Ilja Demuth 10 Elisabeth Steinhagen-Thiessen 10 Anis Larbi 11 Bastian Schilling 12, 13 Dirk Schadendorf 13, 12 Jedd Wolchok 4, 5 Christian Blank 3 Graham Pawelec 1 Claus Garbe 2 Benjamin Weide 2
* Corresponding author
1 Department of Internal Medicine II
2 University of Tübingen
3 The Netherlands Cancer Institute
4 Memorial Sloane Kettering Cancer Center [New York]
5 Weill Medical College of Cornell University [New York]
6 U932 - Immunité et cancer
7 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
8 Service de dermatologie [Nantes]
9 Istituto Nazionale Tumori IRCCS
10 Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin
11 SIgN - Singapore Immunology Network
12 German Cancer Consortium
13 Department of Dermatology
Abstract : 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.
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https://www.hal.inserm.fr/inserm-01408787
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Submitted on : Monday, December 5, 2016 - 1:52:59 PM
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Kilian Wistuba-Hamprecht, Alexander Martens, Karin Haehnel, Marnix Geukes Foppen, Jianda Yuan, et al.. Proportions of blood-borne Vd1þ and Vd2þ T-cells are associated with overall survival of melanoma patients treated with ipilimumab. European Journal of Cancer, Elsevier, 2016, 64, pp.116-126. ⟨10.1016/j.ejca.2016.06.001⟩. ⟨inserm-01408787⟩

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