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Crizotinib-induced immunogenic cell death in non-small cell lung cancer

Author

Listed:
  • Peng Liu

    (University of Paris Sud
    Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer)

  • Liwei Zhao

    (University of Paris Sud
    Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer)

  • Jonathan Pol

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

  • Sarah Levesque

    (University of Paris Sud
    Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer)

  • Adriana Petrazzuolo

    (University of Paris Sud
    Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer)

  • Christina Pfirschke

    (Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School)

  • Camilla Engblom

    (Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School
    Graduate Program in Immunology, Harvard Medical School)

  • Steffen Rickelt

    (Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)

  • Takahiro Yamazaki

    (Weill Cornell Medical College)

  • Kristina Iribarren

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

  • Laura Senovilla

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

  • Lucillia Bezu

    (University of Paris Sud
    Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer)

  • Erika Vacchelli

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

  • Valentina Sica

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

  • Andréa Melis

    (Centre de Recherche INSERM LNC-
    Centre Georges-François Leclerc)

  • Tiffany Martin

    (Centre de Recherche INSERM LNC-
    Centre Georges-François Leclerc)

  • Lin Xia

    (Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College
    Suzhou Institute of Systems Medicine)

  • Heng Yang

    (Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College
    Suzhou Institute of Systems Medicine)

  • Qingqing Li

    (Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College
    Suzhou Institute of Systems Medicine)

  • Jinfeng Chen

    (Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College
    Suzhou Institute of Systems Medicine)

  • Sylvère Durand

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

  • Fanny Aprahamian

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

  • Deborah Lefevre

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

  • Sophie Broutin

    (Institut Gustave Roussy)

  • Angelo Paci

    (Institut Gustave Roussy
    School of Pharmacy, Université Paris Sud)

  • Amaury Bongers

    (Institut Gustave Roussy)

  • Veronique Minard-Colin

    (Institut de Cancérologie, Gustave Roussy Cancer Campus (GRCC))

  • Eric Tartour

    (INSERM U970, Université Paris Descartes Sorbonne Paris-Cité
    Hôpital Européen Georges Pompidou)

  • Laurence Zitvogel

    (University of Paris Sud
    Suzhou Institute of Systems Medicine
    Institut de Cancérologie, Gustave Roussy Cancer Campus (GRCC)
    INSERM U1015)

  • Lionel Apetoh

    (Centre de Recherche INSERM LNC-
    Centre Georges-François Leclerc)

  • Yuting Ma

    (Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College
    Suzhou Institute of Systems Medicine)

  • Mikael J. Pittet

    (Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School
    Massachusetts General Hospital)

  • Oliver Kepp

    (University of Paris Sud
    Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer)

  • Guido Kroemer

    (Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus
    Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers
    Institut National de la Santé et de la Recherche Médicale, UMR1138, Equipe labellisée Ligue Nationale Contre le Cancer
    Université Paris Descartes, Sorbonne Paris Cité)

Abstract

Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10 µM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-γ neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.

Suggested Citation

  • Peng Liu & Liwei Zhao & Jonathan Pol & Sarah Levesque & Adriana Petrazzuolo & Christina Pfirschke & Camilla Engblom & Steffen Rickelt & Takahiro Yamazaki & Kristina Iribarren & Laura Senovilla & Lucil, 2019. "Crizotinib-induced immunogenic cell death in non-small cell lung cancer," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09415-3
    DOI: 10.1038/s41467-019-09415-3
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    Cited by:

    1. Eduardo Moreo & Aitor Jarit-Cabanillas & Iñaki Robles-Vera & Santiago Uranga & Claudia Guerrero & Ana Belén Gómez & Pablo Mata-Martínez & Luna Minute & Miguel Araujo-Voces & María José Felgueres & Glo, 2023. "Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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