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 Hu

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

Cornell University
Université Paris Cité
Université Paris-Saclay
Université Paris-Sud
Sorbonne Université
Sotio
Charles University
Martin Luther University Halle-Wittenberg
Gustave Roussy Cancer Campus
Center of Clinical Investigations in Biotherapies of Cancer (CICBT)
Assistance publique – Hôpitaux de Paris
Institute of Blood Transfusion,Chinese Academy of Medical Sciences& Peking Union Medical College
Karolinska Institutet
Weill Cornell Medical College

Research output: Contribution to journal › Article › peer-review

122 Scopus citations

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
Article number	3819
Pages (from-to)	3819
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17644-0
State	Published - Jul 30 2020
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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

Access to Document

10.1038/s41467-020-17644-0

Cite this

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), 3819. Article 3819. https://doi.org/10.1038/s41467-020-17644-0

@article{fd3b89eebb954c21ba17f4fff4301098,

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.",

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",

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 = jul,

day = "30",

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

language = "English",

volume = "11",

pages = "3819",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

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, no. 1, 3819, pp. 3819. https://doi.org/10.1038/s41467-020-17644-0

TY - JOUR

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 - 2020/7/30

Y1 - 2020/7/30

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.

KW - 9,10-Dimethyl-1,2-benzanthracene

KW - Animals

KW - Breast Neoplasms/immunology

KW - Carcinogenesis/drug effects

KW - Disease Progression

KW - Female

KW - Humans

KW - Immunotherapy/methods

KW - Interferon Type I/immunology

KW - Mammary Neoplasms, Experimental/chemically induced

KW - Medroxyprogesterone Acetate

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Niacinamide/administration & dosage

KW - Receptor, ErbB-2/immunology

KW - Survival Analysis

UR - https://www.scopus.com/pages/publications/85088837105

U2 - 10.1038/s41467-020-17644-0

DO - 10.1038/s41467-020-17644-0

M3 - Article

C2 - 32732875

AN - SCOPUS:85088837105

SN - 2041-1723

VL - 11

SP - 3819

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3819

ER -

Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

Abstract

UN SDGs

Keywords

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