Title | Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Buqué 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 |
Journal | Nat Commun |
Volume | 11 |
Issue | 1 |
Pagination | 3819 |
Date Published | 2020 07 30 |
ISSN | 2041-1723 |
Keywords | 9,10-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 |
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 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. |
DOI | 10.1038/s41467-020-17644-0 |
Alternate Journal | Nat Commun |
PubMed ID | 32732875 |
PubMed Central ID | PMC7393498 |
Grant List | BC180476P1 / / U.S. Department of Defense (United States Department of Defense) / |