2. Academic Validation
  3. Obesity alters monocyte developmental trajectories to enhance metastasis

Obesity alters monocyte developmental trajectories to enhance metastasis

  • J Exp Med. 2023 Aug 7;220(8):e20220509. doi: 10.1084/jem.20220509.
Sheri A C McDowell # 1 2,  Simon Milette # 1 3,  Samuel Doré 1 4,  Miranda W Yu 1 2,  Mark Sorin 1 4,  Liam Wilson 1 2,  Lysanne Desharnais 1 4,  Alyssa Cristea 1 3,  Ozgun Varol 1 3,  Aline Atallah 1 3,  Anikka Swaby 1 3,  Valérie Breton 1,  Azadeh Arabzadeh 1,  Sarah Petrecca 1 3,  Hamza Loucif 5 6,  Aanya Bhagrath 2 6,  Meghan De Meo 7,  Katherine D Lach 8,  Marianne S M Issac 8,  Benoit Fiset 1,  Roni F Rayes 1,  Judith N Mandl 2 5 6,  Jörg H Fritz 5 6,  Pierre O Fiset 8,  Peter R Holt 9,  Andrew J Dannenberg 10,  Jonathan D Spicer 1 3 11,  Logan A Walsh 1 4,  Daniela F Quail 1 2 3
Affiliations

Affiliations

  • 1 Rosalind and Morris Goodman Cancer Institute , Montreal, Canada.
  • 2 Department of Physiology, McGill University, Montreal, Canada.
  • 3 Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Canada.
  • 4 Department of Human Genetics, McGill University, Montreal, Canada.
  • 5 Department of Microbiology and Immunology, McGill University, Montreal, Canada.
  • 6 McGill University Research Centre on Complex Traits , Montreal, Canada.
  • 7 Department of Experimental Surgery, McGill University, Montreal, Canada.
  • 8 Department of Pathology, Faculty of Medicine, McGill University, Montreal, Canada.
  • 9 Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New Nork, NY, USA.
  • 10 Department of Medicine (retired), Weill Cornell Medical College, New York, NY, USA.
  • 11 Department of Surgery, McGill University Health Centre, Montreal, Canada.
  • # Contributed equally.
PMID: 37166450 DOI: 10.1084/jem.20220509
Abstract

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.

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