Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

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Buqué, Aitziber | Bloy, Norma | Perez-Lanzón, Maria | Iribarren, Kristina | Humeau, Juliette | Pol, Jonathan | Levesque, Sarah | Mondragon, Laura | Yamazaki, Takahiro | Sato, Ai | Aranda, Fernando | Durand, Sylvère | Boissonnas, Alexandre | Fucikova, Jitka | Senovilla, Laura | Enot, David | Hensler, Michal | Kremer, Margerie | Stoll, Gautier | Hu, Yang | Massa, Chiara | Formenti, Silvia | Seliger, Barbara | Elemento, Olivier | Spisek, Radek | André, Fabrice | Zitvogel, Laurence | Delaloge, Suzette | Kroemer, Guido | Galluzzi, Lorenzo

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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