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Article Dans Une Revue Nature Communications Année : 2020

Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

Aitziber Buqué
Takahiro Yamazaki
Ai Sato
Fernando Aranda
Jitka Fucikova
  • Fonction : Auteur
Michal Hensler
  • Fonction : Auteur
Gautier Stoll
Yang Hu
Chiara Massa
  • Fonction : Auteur
Silvia Formenti
Barbara Seliger
  • Fonction : Auteur
Olivier Elemento
  • Fonction : Auteur
Radek Spisek
  • Fonction : Auteur
Fabrice André
Laurence Zitvogel
Suzette Delaloge
Guido Kroemer
Lorenzo Galluzzi

Résumé

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.

Domaines

Immunologie
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Dates et versions

hal-03994636 , version 1 (07-03-2024)

Identifiants

Citer

Aitziber Buqué, Norma Bloy, Maria Perez-Lanzón, Kristina Iribarren, Juliette Humeau, et al.. Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer. Nature Communications, 2020, 11, pp.3819. ⟨10.1038/s41467-020-17644-0⟩. ⟨hal-03994636⟩
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