Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

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 Durand, Alexandre Boissonnas, Jitka Fucikova, Laura Senovilla, David Enot, Michal Hensler, Margerie Kremer, Gautier Stoll, Yang Hu, Chiara Massa, Silvia C. Formenti, Barbara Seliger, Olivier Elemento, Radek Spisek, Fabrice André, Laurence Zitvogel, Suzette Delaloge, Guido Kroemer () and Lorenzo Galluzzi ()
Additional contact information
Aitziber Buqué: Weill Cornell Medical College
Norma Bloy: Weill Cornell Medical College
Maria Perez-Lanzón: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Kristina Iribarren: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Juliette Humeau: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Jonathan G. Pol: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Sarah Levesque: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Laura Mondragon: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
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
Sylvère Durand: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Alexandre Boissonnas: Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses CIMI
Jitka Fucikova: Sotio
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
Michal Hensler: Sotio
Margerie Kremer: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Gautier Stoll: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Yang Hu: Caryl and Israel Englander Institute for Precision Medicine
Chiara Massa: Martin Luther University Halle-Wittenberg
Silvia C. Formenti: Weill Cornell Medical College
Barbara Seliger: Martin Luther University Halle-Wittenberg
Olivier Elemento: Caryl and Israel Englander Institute for Precision Medicine
Radek Spisek: Sotio
Fabrice André: Gustave Roussy Cancer Center
Laurence Zitvogel: Université de Paris Sud, Paris-Saclay, Le Kremlin-Bicêtre
Suzette Delaloge: Gustave Roussy Cancer Center
Guido Kroemer: Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université
Lorenzo Galluzzi: Weill Cornell Medical College

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17644-0

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