Posted on October 23, 2020 12:00

breastcancer2020

 

AUTHORS

Aitziber Buqué, Norma Bloy, Maria Perez-Lanzón, Kristina Iribarren, Juliette Humeau, Jonathan G. Pol, Sarah Levesque, Laura Mondragon, Takahiro Yamazaki, Ai Sato, Fernando Aranda, Sylvère Durand, Alexandre Boissonnas, Jitka Fucikova, Laura Senovilla, David Enot, Michal Hensler, Margerie Kremer, Gautier Stoll, Yang Hu, Chiara Massa, Silvia C. Formenti, Barbara Seliger, Olivier Elemento, Radek Spisek, Fabrice André, Laurence Zitvogel, Suzette Delaloge, Guido Kroemer & Lorenzo Galluzzi

 

SUMMARY

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.

REFERENCES

Buqué, A., Bloy, N., Perez-Lanzón, M. et al. Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer. Nat Commun 11, 3819 (2020). https://doi.org/10.1038/s41467-020-17644-0

PRODUCT HIGHLIGHTS

The following Bio X Cell in vivo monoclonal antibodies were featured in the publication: