Peripheral PD-1+CD56+ T-cell frequencies correlate with outcome in stage IV melanoma under PD-1 blockade.

Immune checkpoint blockade with anti-PD-1 antibodies is showing great promise for patients with metastatic melanoma and other malignancies, but despite good responses by some patients who achieve partial or complete regression, many others still do not respond. Here, we sought peripheral blood T-cell biomarker candidates predicting treatment outcome in 75 stage IV melanoma patients treated with anti-PD-1 antibodies. We investigated associations with clinical response, progression-free survival (PFS) and overall survival (OS). Univariate analysis of potential biological confounders and known biomarkers, and a multivariate model, was used to determine statistical independence of associations between candidate biomarkers and clinical outcomes. We found that a lower than median frequency of peripheral PD-1+CD56+ T-cells was associated with longer OS (p = 0.004), PFS (p = 0.041) and superior clinical benefit (p = 0.009). However, neither frequencies of CD56-CD4+ nor CD56-CD8+ T-cells, nor of the PD-1+ fraction within the CD4 or CD8 subsets was associated with clinical outcome. In a multivariate model with known confounders and biomarkers only the M-category (HR, 3.11; p = 0.007) and the frequency of PD-1+CD56+ T-cells (HR, 2.39; p = 0.028) were identified as independent predictive factors for clinical outcome under PD-1 blockade. Thus, a lower than median frequency of peripheral blood PD-1+CD56+ T-cells prior to starting anti-PD-1 checkpoint blockade is associated with superior clinical response, longer PFS and OS of stage IV melanoma patients.

Déclaration de conflit d'intérêts

T. Amaral reports personal fees from Bristol-Myers Squibb, has received travel support from Novartis, Bristol-Myers Squibb, and Merck Sharp & Dahme, outside the submitted work. T. Eigentler reports personal fees from Amgen, BMS, MSD, Roche, Novartis, Pierre Fabre, Sanofi, Leo Pharma outside the submitted work. He is a member of the executive board of the Dermatologic Cooperative Oncology Group (DeCOG). C. Garbe reports receiving commercial research grants from Bristol-Myers Squibb, Novartis, and Roche; and is a consultanUadvisory board member for Amgen, Bristol-Myers Squibb, Merck Sharp & Dahme, Novartis, and Roche. F. Meier reports receiving commercial research grants from Novartis and Roche; and has received travel support or/and speaker’ s fees or/and advisor’s honoraria from Novartis, Roche, Bristol-Myers Squibb, Merck Sharp & Dahme, and Pierre Fabre. G. Pawelec has received research support from lmmatics Biotechnologies GmbH, speaker’s honoraria from Celgene, Pfizer, Sanofi, 4D-Pharma, Clasado, and Seqirus and is a Consultant to Repair Biotechnologies, Inc. P. Terheyden has received speaker’ s honoraria from Bristol-Myers Squibb, Novartis, and Roche, consultant’s honoraria from Bristol-Myers Squibb, Merck Serano, Novartis, Pierre Fabre, Sanofi, and Roche and travel support from Bristol-Myers Squibb and Pierre Fabre. B. Weide reports receiving commercial research grants from, and is a consultanUadvisory board member for, and reports receiving travel reimbursement from Bristol-Myers Squibb and Merck Sharp & Dohme. K. Wistuba-Hamprecht holds a visiting research association at King’s College London and receives commercial research grants from the Catalym GmbH. H. Zelba contributed to this manuscript while he was employed by the University Medical Center Tubingen. He is meanwhile an employee of the CeGat GmbH. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.