Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 30, 2020
- Source ID
- 10.1038/s41467-020-17644-0
Entities
People
- Ai Sato
- Aitziber Buqué
- Alexandre Boissonnas
- Barbara Seliger
- Chiara Massa
- David Enot
- Fabrice André
- Fernando Aranda
- Gautier Stoll
- Guido Kroemer
- Jitka Fucikova
- Jonathan G Pol
- Juliette Humeau
- Kristina Iribarren
- Laura Mondragon
- Laura Senovilla
- Laurence Zitvogel
- Lorenzo Galluzzi
- Margerie Kremer
- Maria Perez-lanzón
- Michal Hensler
- Norma Bloy
- Olivier Elemento
- Radek Spisek
- Sarah Levesque
- Silvia C. Formenti
- Suzette Delaloge
- Sylvère Durand
- Takahiro Yamazaki
- Yang Hu
Organizations
- United States Department of Defense