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Predictors of responses to immune checkpoint blockade in advanced melanoma

Author

Listed:
  • N. Jacquelot

    (Gustave Roussy Cancer Campus
    University Paris-Saclay
    Gustave Roussy Cancer Campus)

  • M. P. Roberti

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • D. P. Enot

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • S. Rusakiewicz

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • N. Ternès

    (University Paris-Saclay
    Gustave Roussy Cancer Campus
    Université Paris-Saclay, Service de Biostatistique et d’Epidémiologie)

  • S. Jegou

    (Saint Antoine Hospital)

  • D. M. Woods

    (New York University Medical Center)

  • A. L. Sodré

    (New York University Medical Center)

  • M. Hansen

    (Copenhagen University Hospital)

  • Y. Meirow

    (The Hebrew University Hadassah Medical School)

  • M. Sade-Feldman

    (The Hebrew University Hadassah Medical School)

  • A. Burra

    (University of California)

  • S. S. Kwek

    (University of California)

  • C. Flament

    (Gustave Roussy Cancer Campus
    University Paris-Saclay
    Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • M. Messaoudene

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • C. P. M. Duong

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • L. Chen

    (Yale School of Medicine)

  • B. S. Kwon

    (Eutilex
    Tulane University Health Sciences Center)

  • A. C. Anderson

    (Brigham and Women’s Hospital and Harvard Medical School)

  • V. K. Kuchroo

    (Brigham and Women’s Hospital and Harvard Medical School)

  • B. Weide

    (University Medical Center Tübingen)

  • F. Aubin

    (Université de Franche Comté, EA3181, SFR4234, Service de Dermatologie, Centre Hospitalier Universitaire (CHU))

  • C. Borg

    (University Hospital of Besancon
    University Hospital of Besançon
    University of Franche-Comté)

  • S. Dalle

    (Hospices Civils de Lyon and University Claude Bernard Lyon 1
    Centre de Recherche en Cancérologie de Lyon)

  • O. Beatrix

    (Hospices Civils de Lyon and University Claude Bernard Lyon 1)

  • M. Ayyoub

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • B. Balme

    (Hospices Civils de Lyon and University Claude Bernard Lyon 1
    Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon)

  • G. Tomasic

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • A. M. Giacomo

    (University Hospital of Siena)

  • M. Maio

    (University Hospital of Siena, Instituto Toscano Tumori)

  • D. Schadendorf

    (University Hospital, University Duisburg-Essen, Essen, Germany & German Cancer Consortium (DKTZ))

  • I. Melero

    (Centre for Applied Medical Research
    University Clinic of Navarra
    Centro de Investigación cBiomedica en Red de Oncologia)

  • B. Dréno

    (CIC Biotherapy)

  • A. Khammari

    (CIC Biotherapy)

  • R. Dummer

    (University Hospital Zürich and University of Zürich)

  • M. Levesque

    (University Hospital Zürich and University of Zürich)

  • Y. Koguchi

    (Providence Cancer Center)

  • L. Fong

    (University of California)

  • M. Lotem

    (Hadassah Medical Organization)

  • M. Baniyash

    (The Hebrew University Hadassah Medical School)

  • H. Schmidt

    (Aarhus University Hospital)

  • I. M. Svane

    (Copenhagen University Hospital)

  • G. Kroemer

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus
    Centre de Recherche des Cordeliers
    Centre de Recherche des Cordeliers)

  • A. Marabelle

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

  • S. Michiels

    (Gustave Roussy Cancer Campus
    Université Paris-Saclay, Service de Biostatistique et d’Epidémiologie)

  • A. Cavalcanti

    (Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Center
    Gustave Roussy Cancer Center)

  • M. J. Smyth

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

  • J. S. Weber

    (New York University Medical Center)

  • A. M. Eggermont

    (Gustave Roussy Cancer Campus)

  • L. Zitvogel

    (Gustave Roussy Cancer Campus
    University Paris-Saclay
    Gustave Roussy Cancer Campus
    Gustave Roussy Cancer Campus)

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.

Suggested Citation

  • N. Jacquelot & M. P. Roberti & D. P. Enot & S. Rusakiewicz & N. Ternès & S. Jegou & D. M. Woods & A. L. Sodré & M. Hansen & Y. Meirow & M. Sade-Feldman & A. Burra & S. S. Kwek & C. Flament & M. Messao, 2017. "Predictors of responses to immune checkpoint blockade in advanced melanoma," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00608-2
    DOI: 10.1038/s41467-017-00608-2
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    Cited by:

    1. Isabella Pallavicini & Teresa Maria Frasconi & Carlotta Catozzi & Elena Ceccacci & Silvia Tiberti & Dorothee Haas & Jule Samson & Christoph Heuser-Loy & Carina B. Nava Lauson & Marta Mangione & Elisa , 2024. "LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+ T cell responsiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Dzana Dervovic & Ahmad A. Malik & Edward L. Y. Chen & Masahiro Narimatsu & Nina Adler & Somaieh Afiuni-Zadeh & Dagmar Krenbek & Sebastien Martinez & Ricky Tsai & Jonathan Boucher & Jacob M. Berman & K, 2023. "In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Filipa Lynce & Candace Mainor & Renee N. Donahue & Xue Geng & Greg Jones & Ilana Schlam & Hongkun Wang & Nicole J. Toney & Caroline Jochems & Jeffrey Schlom & Jay Zeck & Christopher Gallagher & Rita N, 2024. "Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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