作者
Sheri A C McDowell,Simon Milette,Samuel Doré,Miranda W. Yu,Mark Sorin,Liam R. Wilson,Lysanne Desharnais,A Cristea,Ozgun Varol,Aline Atallah,Anikka Swaby,Valérie Breton,Azadeh Arabzadeh,Sarah Petrecca,Hamza Loucif,Aanya Bhagrath,Marianna Meo,Katherine Lach,Marianne Samir Makboul Issac,Benoit Fiset,Roni F. Rayes,Judith N. Mandl,Jörg H. Fritz,Pierre‐Olivier Fiset,Peter R. Holt,Andrew J. Dannenberg,Jonathan Spicer,Logan A. Walsh,Daniela F. Quail
摘要
Obesity is characterized by chronic systemic inflammation and enhances cancer metastasis and mortality. Obesity promotes breast cancer metastasis to lung in a neutrophil-dependent manner; however, the upstream regulatory mechanisms of this process remain unknown. Here, we show that obesity-induced monocytes underlie neutrophil activation and breast cancer lung metastasis. Using mass cytometry, obesity favors the expansion of myeloid lineages while restricting lymphoid cells within the peripheral blood. RNA sequencing and flow cytometry revealed that obesity-associated monocytes resemble professional antigen-presenting cells due to a shift in their development and exhibit enhanced MHCII expression and CXCL2 production. Monocyte induction of the CXCL2–CXCR2 axis underlies neutrophil activation and release of neutrophil extracellular traps to promote metastasis, and enhancement of this signaling axis is observed in lung metastases from obese cancer patients. Our findings provide mechanistic insight into the relationship between obesity and cancer by broadening our understanding of the interactive role that myeloid cells play in this process.