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Article Dans Une Revue Nature Communications Année : 2017

Predictors of responses to immune checkpoint blockade in advanced melanoma

1 UMR 1015 - Immunologie des tumeurs et immunothérapie
2 Université Paris-Saclay
3 IGR - Institut Gustave Roussy
4 Plateforme de métabolomique
5 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers
6 SBE - Service de biostatistique et d'épidémiologie
7 ERL INSERM U1157 - CNRS UMR 7203 - Microorganismes et physiopathologie intestinale
8 Laura & Isaac Perlmutter Cancer Center [New York, NY, USA]
9 Department of Hematology and Oncology [Herlev, Denmark]
10 The Lautenberg Center for General and Tumor Immunology [Jerusalem, Israel]
11 Department of Medicine - Division of Hematology-Oncology [San Francisco, CA, USA]
12 Yale School of Medicine - Department of Immunobiology [New Haven, CT, USA]
13 Eutilex Co., Ltd [Seoul, Korea]
14 Department of Medicine - Section of Clinical Immunology, Allergy, and Rheumatology [New Orleans, LA, USA]
15 Ann Romney Center for Neurologic Diseases - Evergrande Center for Immunologic Diseases [Boston, MA, USA]
16 Department of Dermatology [Tubingen, Germany]
17 CEF2P / CARCINO - Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181)
18 Service d'Oncologie Médicale [CHRU Besançon]
19 Inserm CIC 1431 - Centre d'Investigation Clinique de Besançon
20 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
21 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
22 UCBL - Université Claude Bernard Lyon 1
23 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
24 Département de Pathologie [CHU Lyon-Sud - HCL]
25 Département de biologie et pathologie médicales [Gustave Roussy]
26 Division of Medical Oncology and Immunotherapy [Siena, Italy]
27 Department of Dermatology [Essen, Germany]
28 CIMA - Division of Hepatology and Gene Therapy
29 Oncology Department [Pamplona, Spain]
30 CIBERO - Centro de Investigación Biomedica en Red de Oncologia [Pamplona, Spain]
31 CRCINA-ÉQUIPE 2 - Clinical and Translational Research in Skin Cancer
32 UZH - Universität Zürich [Zürich] = University of Zurich
33 Earle A. Chiles Research Institute [Portland, OR, USA]
34 Sharett Institute of Oncology [Jerusalem, Israel]
35 Department of Oncology [Aarhus, Denmark]
36 CRC - Centre de Recherche des Cordeliers
37 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
38 USPC - Université Sorbonne Paris Cité
39 Pôle de biologie
40 Département de chirurgie générale [Gustave Roussy]
41 Service de dermatologie
42 Immunology in Cancer and Infection Laboratory [Herston, QLD, Australia]
43 School of Medicine [Herston, QLD, Australia]
Lin Chen

Résumé

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.

Domaines

Cancer
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Dates et versions

inserm-01824289 , version 1 (27-06-2018)

Identifiants

Citer

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, 2017, 8 (1), pp.592. ⟨10.1038/s41467-017-00608-2⟩. ⟨inserm-01824289⟩
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