Immunoprophylactic and Immunotherapeutic Control of Hormone Receptor-positive Breast Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Aug 1

PMID 32732875

Citations 52

Authors

Aitziber Buque

Norma Bloy

Maria Perez-Lanzon

Kristina Iribarren

Juliette Humeau

Jonathan G Pol

Sarah Levesque

Laura Mondragon

Takahiro Yamazaki

Ai Sato

Fernando Aranda

Sylvere 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 Andre

Laurence Zitvogel

Suzette Delaloge

Guido Kroemer

Lorenzo Galluzzi

Affiliations

Soon will be listed here.

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 HRHER2 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.

Citing Articles

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