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Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

Author

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  • Aitziber Buqué

    (Weill Cornell Medical College
    Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université)

  • Norma Bloy

    (Weill Cornell Medical College
    Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université)

  • Maria Perez-Lanzón

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Université de Paris Sud, Paris-Saclay, Le Kremlin-Bicêtre
    Gustave Roussy Comprehensive Cancer Institute)

  • Kristina Iribarren

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute)

  • Juliette Humeau

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Université de Paris Sud, Paris-Saclay, Le Kremlin-Bicêtre
    Gustave Roussy Comprehensive Cancer Institute)

  • Jonathan G. Pol

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute)

  • Sarah Levesque

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Université de Paris Sud, Paris-Saclay, Le Kremlin-Bicêtre
    Gustave Roussy Comprehensive Cancer Institute)

  • Laura Mondragon

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute)

  • Takahiro Yamazaki

    (Weill Cornell Medical College)

  • Ai Sato

    (Weill Cornell Medical College)

  • Fernando Aranda

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute)

  • Sylvère Durand

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute)

  • Alexandre Boissonnas

    (Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses CIMI)

  • Jitka Fucikova

    (Sotio
    Charles University, 2nd Faculty of Medicine and University Hospital Motol)

  • Laura Senovilla

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université)

  • David Enot

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute)

  • Michal Hensler

    (Sotio)

  • Margerie Kremer

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute)

  • Gautier Stoll

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute)

  • Yang Hu

    (Caryl and Israel Englander Institute for Precision Medicine)

  • Chiara Massa

    (Martin Luther University Halle-Wittenberg)

  • Silvia C. Formenti

    (Weill Cornell Medical College
    Sandra and Edward Meyer Cancer Center)

  • Barbara Seliger

    (Martin Luther University Halle-Wittenberg)

  • Olivier Elemento

    (Caryl and Israel Englander Institute for Precision Medicine
    Sandra and Edward Meyer Cancer Center)

  • Radek Spisek

    (Sotio
    Charles University, 2nd Faculty of Medicine and University Hospital Motol)

  • Fabrice André

    (Gustave Roussy Cancer Center)

  • Laurence Zitvogel

    (Université de Paris Sud, Paris-Saclay, Le Kremlin-Bicêtre
    Gustave Roussy Cancer Center
    INSERM U1015
    Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428)

  • Suzette Delaloge

    (Gustave Roussy Cancer Center)

  • Guido Kroemer

    (Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
    Gustave Roussy Comprehensive Cancer Institute
    Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP
    Chinese Academy of Medical Sciences)

  • Lorenzo Galluzzi

    (Weill Cornell Medical College
    Caryl and Israel Englander Institute for Precision Medicine
    Sandra and Edward Meyer Cancer Center
    Yale School of Medicine)

Abstract

Hormone receptor (HR)+ breast cancer (BC) causes most BC-related deaths, calling for improved therapeutic approaches. Despite expectations, immune checkpoint blockers (ICBs) are poorly active in patients with HR+ BC, in part reflecting the lack of preclinical models that recapitulate disease progression in immunocompetent hosts. We demonstrate that mammary tumors driven by medroxyprogesterone acetate (M) and 7,12-dimethylbenz[a]anthracene (D) recapitulate several key features of human luminal B HR+HER2− BC, including limited immune infiltration and poor sensitivity to ICBs. M/D-driven oncogenesis is accelerated by immune defects, demonstrating that M/D-driven tumors are under immunosurveillance. Safe nutritional measures including nicotinamide (NAM) supplementation efficiently delay M/D-driven oncogenesis by reactivating immunosurveillance. NAM also mediates immunotherapeutic effects against established M/D-driven and transplantable BC, largely reflecting increased type I interferon secretion by malignant cells and direct stimulation of immune effector cells. Our findings identify NAM as a potential strategy for the prevention and treatment of HR+ BC.

Suggested Citation

  • Aitziber Buqué & Norma Bloy & Maria Perez-Lanzón & Kristina Iribarren & Juliette Humeau & Jonathan G. Pol & Sarah Levesque & Laura Mondragon & Takahiro Yamazaki & Ai Sato & Fernando Aranda & Sylvère D, 2020. "Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17644-0
    DOI: 10.1038/s41467-020-17644-0
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