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

TitleImmunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer.
Publication TypeJournal Article
Year of Publication2020
AuthorsBuqué A, Bloy N, Perez-Lanzón M, Iribarren K, Humeau J, Pol JG, Levesque S, Mondragon L, Yamazaki T, Sato A, Aranda F, Durand S, Boissonnas A, Fucikova J, Senovilla L, Enot D, Hensler M, Kremer M, Stoll G, Hu Y, Massa C, Formenti SC, Seliger B, Elemento O, Spisek R, André F, Zitvogel L, Delaloge S, Kroemer G, Galluzzi L
JournalNat Commun
Date Published2020 07 30
Keywords9,10-Dimethyl-1,2-benzanthracene, Animals, Breast Neoplasms, Carcinogenesis, Disease Progression, Female, Humans, Immunotherapy, Interferon Type I, Mammary Neoplasms, Experimental, Medroxyprogesterone Acetate, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Niacinamide, Receptor, ErbB-2, Survival Analysis

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 HRHER2 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.

Alternate JournalNat Commun
PubMed ID32732875
PubMed Central IDPMC7393498
Grant ListBC180476P1 / / U.S. Department of Defense (United States Department of Defense) /