Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

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

doi:10.1038/s41467-020-17644-0

Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

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 HuChiara Massa, Silvia C. Formenti, Barbara Seliger, Olivier Elemento, Radek Spisek, Fabrice André, Laurence Zitvogel, Suzette Delaloge, Guido Kroemer, Lorenzo Galluzzi

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

84 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Numéro d'article	3819
journal	Nature Communications
Volume	11
Numéro de publication	1
Les DOIs	https://doi.org/10.1038/s41467-020-17644-0
état	Publié - 1 déc. 2020

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10.1038/s41467-020-17644-0

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Buqué, A., Bloy, N., Perez-Lanzón, M., Iribarren, K., Humeau, J., Pol, J. G., 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., ... Galluzzi, L. (2020). Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer. Nature Communications, 11(1), Article 3819. https://doi.org/10.1038/s41467-020-17644-0

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title = "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.",

author = "Aitziber Buqu{\'e} and Norma Bloy and Maria Perez-Lanz{\'o}n and Kristina Iribarren and Juliette Humeau and Pol, {Jonathan G.} and Sarah Levesque and Laura Mondragon and Takahiro Yamazaki and Ai Sato and Fernando Aranda and Sylv{\`e}re Durand and Alexandre Boissonnas and Jitka Fucikova and Laura Senovilla and David Enot and Michal Hensler and Margerie Kremer and Gautier Stoll and Yang Hu and Chiara Massa and Formenti, {Silvia C.} and Barbara Seliger and Olivier Elemento and Radek Spisek and Fabrice Andr{\'e} and Laurence Zitvogel and Suzette Delaloge and Guido Kroemer and Lorenzo Galluzzi",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-17644-0",

language = "English",

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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 2020, 'Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer', Nature Communications, VOL. 11, Numéro 1, 3819. https://doi.org/10.1038/s41467-020-17644-0

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T1 - Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

AU - Buqué, Aitziber

AU - Bloy, Norma

AU - Perez-Lanzón, Maria

AU - Iribarren, Kristina

AU - Humeau, Juliette

AU - Pol, Jonathan G.

AU - Levesque, Sarah

AU - Mondragon, Laura

AU - Yamazaki, Takahiro

AU - Sato, Ai

AU - Aranda, Fernando

AU - Durand, Sylvère

AU - Boissonnas, Alexandre

AU - Fucikova, Jitka

AU - Senovilla, Laura

AU - Enot, David

AU - Hensler, Michal

AU - Kremer, Margerie

AU - Stoll, Gautier

AU - Hu, Yang

AU - Massa, Chiara

AU - Formenti, Silvia C.

AU - Seliger, Barbara

AU - Elemento, Olivier

AU - Spisek, Radek

AU - André, Fabrice

AU - Zitvogel, Laurence

AU - Delaloge, Suzette

AU - Kroemer, Guido

AU - Galluzzi, Lorenzo

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-020-17644-0

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