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.
Original language | English |
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Article number | 3819 |
Pages (from-to) | 3819 |
Journal | Nature Communications |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - Jun 30 2020 |
Externally published | Yes |
Keywords
- 9,10-Dimethyl-1,2-benzanthracene
- Animals
- Breast Neoplasms/immunology
- Carcinogenesis/drug effects
- Disease Progression
- Female
- Humans
- Immunotherapy/methods
- Interferon Type I/immunology
- Mammary Neoplasms, Experimental/chemically induced
- Medroxyprogesterone Acetate
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Niacinamide/administration & dosage
- Receptor, ErbB-2/immunology
- Survival Analysis