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Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer.

Aitziber BuqueNorma BloyMaria Perez-LanzónKristina IribarrenJuliette HumeauJonathan G PolSarah LevesqueLaura MondragonTakahiro YamazakiAi SatoFernando ArandaSylvère DurandAlexandre BoissonnasJitka FucikovaLaura SenovillaDavid EnotMichal HenslerMargerie KremerGautier StollYang HuChiara MassaSylvia C FormentiBarbara SeligerOlivier ElementoRadek SpisekFabrice AndreLaurence ZitvogelSuzette DelalogeGuido KroemerLorenzo Galluzzi
Published in: Nature communications (2020)
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.
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