Journal article 651 views 68 downloads
Tumour-elicited neutrophils engage mitochondrial metabolism to circumvent nutrient limitations and maintain immune suppression
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Jeff J. Subleski,
Nunziata Maio,
Marieli Gonzalez-Cotto,
Caroline Andrews,
Nimit L. Patel,
Erika M. Palmieri,
Jonathan M. Weiss,
Jung-Min Lee,
Christina M. Annunziata,
Tracey A. Rouault,
Scott K. Durum,
Daniel W. McVicar
Nature Communications, Volume: 9, Issue: 1
Swansea University Author:
Luke Davies
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DOI (Published version): 10.1038/s41467-018-07505-2
Abstract
Neutrophils are a vital component of immune protection, yet in cancer they may promote tumour progression, partly by generating reactive oxygen species (ROS) that disrupts lymphocyte functions. Metabolically, neutrophils are often discounted as purely glycolytic. Here we show that immature, c-Kit+ n...
| Published in: | Nature Communications |
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| ISSN: | 2041-1723 |
| Published: |
Springer Science and Business Media LLC
2018
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa61701 |
| Abstract: |
Neutrophils are a vital component of immune protection, yet in cancer they may promote tumour progression, partly by generating reactive oxygen species (ROS) that disrupts lymphocyte functions. Metabolically, neutrophils are often discounted as purely glycolytic. Here we show that immature, c-Kit+ neutrophils subsets can engage in oxidative mitochondrial metabolism. With limited glucose supply, oxidative neutrophils use mitochondrial fatty acid oxidation to support NADPH oxidase-dependent ROS production. In 4T1 tumour-bearing mice, mitochondrial fitness is enhanced in splenic neutrophils and is driven by c-Kit signalling. Concordantly, tumour-elicited oxidative neutrophils are able to maintain ROS production and T cell suppression when glucose utilisation is restricted. Consistent with these findings, peripheral blood neutrophils from patients with cancer also display increased immaturity, mitochondrial content and oxidative phosphorylation. Together, our data suggest that the glucose-restricted tumour microenvironment induces metabolically adapted, oxidative neutrophils to maintain local immune suppression. |
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| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
This work has been funded with federal funds from the National Cancer Institute, National Institutes of Health, Intramural Research Program, USA. L.C.D. is funded by the Henry Wellcome Trust, UK (WT103973MA). |
| Issue: |
1 |