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dc.contributor.authorPetruzzelli, Michele
dc.contributor.authorFerrer, Miriam
dc.contributor.authorSchuijs, Martijn J
dc.contributor.authorKleeman, Sam O
dc.contributor.authorMourikis, Nicholas
dc.contributor.authorHall, Zoe
dc.contributor.authorPerera, David
dc.contributor.authorRaghunathan, Shwethaa
dc.contributor.authorVacca, Michele
dc.contributor.authorGaude, Edoardo
dc.contributor.authorLukey, Michael J
dc.contributor.authorJodrell, Duncan
dc.contributor.authorFrezza, Christian
dc.contributor.authorWagner, Erwin F
dc.contributor.authorVenkitaraman, Ashok R
dc.contributor.authorHalim, Timotheus
dc.contributor.authorJanowitz, Tobias
dc.date.accessioned2022-02-17T09:00:26Z
dc.date.available2022-02-17T09:00:26Z
dc.date.issued2022-02-15
dc.identifier.issn2072-6694
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334144
dc.description.abstractAn elevated neutrophil-lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells. Although pharmacological inhibition of aerobic glycolysis slows down tumor growth in C26 tumor-bearing mice, it precipitates cachexia, thereby shortening the overall survival. This negative effect may be explained by our observation that acute depletion of neutrophils in pre-cachectic mice impairs systemic glucose homeostasis secondary to altered hepatic lipid processing. Thus, changes in neutrophil number, distribution, and metabolism play an adaptive role in host metabolic homeostasis during cancer progression. Our findings provide insight into early events during cancer progression to cachexia, with implications for therapy.
dc.languageen
dc.publisherMDPI AG
dc.subjectcancer
dc.subjectcachexia
dc.subjectmetabolism
dc.subjecthost
dc.subjectneutrophils
dc.subjectaerobic glycolysis
dc.titleEarly Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia.
dc.typeArticle
dc.date.updated2022-02-17T09:00:26Z
prism.issueIdentifier4
prism.publicationNameCancers (Basel)
prism.volume14
dc.identifier.doi10.17863/CAM.81554
dcterms.dateAccepted2022-02-09
rioxxterms.versionofrecord10.3390/cancers14040963
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidFerrer, Miriam [0000-0002-5589-975X]
dc.contributor.orcidVacca, Michele [0000-0002-1973-224X]
dc.contributor.orcidGaude, Edoardo [0000-0001-8523-7792]
dc.contributor.orcidJodrell, Duncan [0000-0001-9360-1670]
dc.contributor.orcidHalim, Timotheus [0000-0001-9773-0023]
dc.identifier.eissn2072-6694
pubs.funder-project-idMedical Research Council (MC_UU_12022/1)
pubs.funder-project-idMRC (MC_UU_12022/8)
cam.issuedOnline2022-02-15


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