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.

Caryl and Israel Englander Institute for Precision Medicine New York NY USA

Center of Clinical Investigations in Biotherapies of Cancer 1428 Villejuif France

Department of Cancer Medicine Gustave Roussy Cancer Center Villejuif France

Department of Dermatology Yale School of Medicine New Haven CT USA

Department of Immunology Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Department of Radiation Oncology Weill Cornell Medical College New York NY USA

Department of Women's and Children's Health Karolinska University Hospital Stockholm Sweden

Equipe labellisée par la Ligue contre le cancer Centre de Recherche des Cordeliers INSERM U1138 Université de Paris Sorbonne Université Paris France

Faculté de Médecine Université de Paris Sud Paris Saclay Le Kremlin Bicêtre Paris France

Gustave Roussy Cancer Center Villejuif France

INSERM U1015 Villejuif France

Institute of Medical Immunology Martin Luther University Halle Wittenberg Halle Germany

Metabolomics and Cell Biology Platforms Gustave Roussy Comprehensive Cancer Institute Villejuif France

Pôle de Biologie Hôpital Européen Georges Pompidou AP HP Paris France

Sandra and Edward Meyer Cancer Center New York NY USA

Sorbonne Université Inserm CNRS Centre d'Immunologie et des Maladies Infectieuses CIMI Paris France

Sotio Prague Czech Republic

Suzhou Institute for Systems Medicine Chinese Academy of Medical Sciences Suzhou China

Université de Paris Paris France

Erratum v

Nat Commun. 2020 Sep 17;11(1):4787. doi: 10.1038/s41467-020-18719-8. PubMed

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