King's College London

Research portal

Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer

Research output: Contribution to journalArticle

Payal Tiwari, Ariane Blank, Chang Cui, Kelly Q. Schoenfelt, Guolin Zhou, Yanfei Xu, Galina Khramtsova, Funmi Olopade, Ajay M. Shah, Seema A. Khan, Marsha Rich Rosner, Lev Becker

Original languageEnglish
Pages (from-to)1345-1358
Number of pages14
JournalThe Journal of experimental medicine
Issue number6
Publication statusPublished - 3 Jun 2019

King's Authors


Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice. MMe macrophages release IL-6 in an NADPH oxidase 2 (NOX2)-dependent manner, which signals through glycoprotein 130 (GP130) on TNBC cells to promote stem-like properties including tumor formation. Deleting Nox2 in myeloid cells or depleting GP130 in TNBC cells attenuates obesity-augmented TNBC stemness. Moreover, weight loss reverses the effects of obesity on MMe macrophage inflammation and TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue as a mechanism for promoting TNBC stemness and tumorigenesis during obesity.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454