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


Bochem J1, Zelba H1, Amaral T1,2, Spreuer J1, Soffel D1, Eigentler T1, Wagner NB1, Uslu U3, Terheyden P4, Meier F5,6, Garbe C1, Pawelec G7,8,9,10,11, Weide B1, Wistuba-Hamprecht K1.
  1. Department of Dermatology, University Medical Center, Tübingen, Germany.
  2. Portuguese Air Force Health Direction, Lisbon, Portugal.
  3. Department of Dermatology, Friedrich-Alexander-University of Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, Erlangen, Germany.
  4. Department of Dermatology, University of Lübeck, Lübeck, Germany.
  5. Skin Cancer Center at the University Cancer Centre, Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
  6. National Center for Tumor Diseases (NCT), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  7. Department of Immunology, University of Tübingen, Tübingen, Germany.
  8. Health Sciences North Research Institute, Sudbury, Ontario, Canada.
  9. Division of Cancer Studies, King’s College London, London, United Kingdom.
  10. John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, United Kingdom.
  11. Institute of Cancer Sciences, Manchester University, Manchester, United Kingdom.


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.