Predictors of responses to immune checkpoint blockade in advanced melanoma

N. Jacquelot 1, 2, 3 M.P. Roberti 1, 3 D.P. Enot 3, 4 S. Rusakiewicz 1, 3, 5 N. Ternès 2, 3, 6 S. Jegou 7 D.M. Woods 8 A.L. Sodré 8 M. Hansen 9 Y. Meirow 10 M. Sade-Feldman 10 A. Burra 11 S.S. Kwek 11 C. Flament 1, 2, 3, 5 M. Messaoudene 1, 3 C.P.M. Duong 1, 3 Lin Chen 12 B.S. Kwon 13, 14 A.C. Anderson 15 V.K. Kuchroo 15 B. Weide 16 F. Aubin 17 C. Borg 18, 19, 20 S. Dalle 21, 22, 23 O. Beatrix 22, 21 M. Ayyoub 1, 3 B. Balme 21, 22, 24 G. Tomasic 3, 25 A.M. Di Giacomo 26 M. Maio 26 D. Schadendorf 27 I. Melero 28, 29, 30 Brigitte Dréno 31 Amir Khammari 31 R. Dummer 32 M. Levesque 32 Y. Koguchi 33 L. Fong 11 M. Lotem 34 M. Baniyash 10 H. Schmidt 35 I.M. Svane 9 G. Kroemer 3, 4, 36, 37, 38, 39 A. Marabelle 1, 3, 5 S. Michiels 3, 6 A. Cavalcanti 3, 40, 41 M.J. Smyth 42, 43 J.S. Weber 8 A.M. Eggermont 3 Laurence Zitvogel 1, 2, 3, 5, 6, *
* Corresponding author
4 Plateforme de métabolomique
Direction de la recherche [Gustave Roussy]
31 CRCINA - Département INCIT - Equipe 2 - Clinical and translational research in skin cancer
CRCINA - Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers
37 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
IGR - Institut Gustave Roussy, CRC - Centre de Recherche des Cordeliers
41 Service de dermatologie
Département de médecine oncologique [Gustave Roussy]
Abstract : 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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N. Jacquelot, M.P. Roberti, D.P. Enot, S. Rusakiewicz, N. Ternès, et al.. Predictors of responses to immune checkpoint blockade in advanced melanoma. Nature Communications, Nature Publishing Group, 2017, 8 (1), pp.592. ⟨10.1038/s41467-017-00608-2⟩. ⟨inserm-01824289⟩

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