Article open access publication

Predictors of responses to immune checkpoint blockade in advanced melanoma

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 8, 1, 2017

DOI:10.1038/s41467-017-00608-2, Dimensions: pub.1091688617, PMC: PMC5605517, PMID: 28928380,

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  1. (1) Institut Gustave Roussy, grid.14925.3b
  2. (2) University of Paris-Saclay, grid.460789.4
  3. (3) Hôpital Saint-Antoine, grid.412370.3
  4. (4) New York University Langone Medical Center, grid.240324.3
  5. (5) Herlev Hospital, grid.411900.d, Capital Region
  6. (6) Hebrew University of Jerusalem, grid.9619.7
  7. (7) University of California, San Francisco, grid.266102.1
  8. (8) Yale University, grid.47100.32
  9. (9) Eutilex, Suite# 1401 Daeryung Technotown 17 Gasan Digital 1-ro 25, 08594, Geumcheon-gu, Seoul, Korea
  10. (10) Tulane University, grid.265219.b
  11. (11) Harvard University, grid.38142.3c
  12. (12) Universitätsklinikum Tübingen, grid.411544.1
  13. (13) Université de Franche Comté, EA3181, SFR4234, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), 25000, Besançon, France
  14. (14) Centre Hospitalier Universitaire de Besançon, grid.411158.8
  15. (15) University of Franche-Comté, grid.7459.f
  16. (16) Cancer Center of Lyon, grid.462282.8
  17. (17) Centre Hospitalier Lyon Sud, grid.411430.3
  18. (18) Hospices Civils de Lyon, grid.413852.9
  19. (19) Azienda Ospedaliera Universitaria Senese, grid.411477.0
  20. (20) University of Duisburg-Essen, grid.5718.b
  21. (21) Centro de Investigación cBiomedica en Red de Oncologia, 31008, Pamplona, Spain
  22. (22) Clinica Universidad de Navarra, grid.411730.0
  23. (23) Division of Gene Therapy and Hepatology, Centre for Applied Medical Research, 31008, Pamplona, Spain
  24. (24) Centre Hospitalier Universitaire de Nantes, grid.277151.7
  25. (25) Department of Dermatology, University Hospital Zürich and University of Zürich, 8091, Zürich, Switzerland
  26. (26) Earle A. Chiles Research Institute, Providence Cancer Center, 97213, Portland, OR, USA
  27. (27) Hadassah Medical Center, grid.17788.31
  28. (28) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  29. (29) Centre de Recherche des Cordeliers, grid.417925.c
  30. (30) Hôpital Européen Georges-Pompidou, grid.414093.b
  31. (31) Paris Descartes University, grid.10992.33
  32. (32) Sorbonne University, grid.462844.8
  33. (33) Department of Dermatology, Gustave Roussy Cancer Center, 94800, Villejuif, France
  34. (34) Department of Surgery, Gustave Roussy Cancer Center, 94800, Villejuif, France
  35. (35) QIMR Berghofer Medical Research Institute, grid.1049.c
  36. (36) University of Queensland, grid.1003.2

Description

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

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Danish Open Access Indicator

2017: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2017: Level 2

Research area: Medicine

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Times Cited: 90

Field Citation Ratio (FCR): 24.08

Relative Citation ratio (RCR): 5.63

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