{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:55:44Z","timestamp":1787320544285,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["Clinical Lecturer Fellowship"],"award-info":[{"award-number":["Clinical Lecturer Fellowship"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["Clinical Lecturer"],"award-info":[{"award-number":["Clinical Lecturer"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"La Caixa Foundation","award":["100010434"],"award-info":[{"award-number":["100010434"]}]},{"name":"MRC Cancer Unit","award":["MRC CU Research Studentship"],"award-info":[{"award-number":["MRC CU Research Studentship"]}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C42738\/A24868"],"award-info":[{"award-number":["C42738\/A24868"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A24995"],"award-info":[{"award-number":["A24995"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013356","name":"Cold Spring Harbor Laboratory","doi-asserted-by":"publisher","award":["5P30CA045508"],"award-info":[{"award-number":["5P30CA045508"]}],"id":[{"id":"10.13039\/100013356","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014599","name":"The Mark Foundation for Cancer Research","doi-asserted-by":"publisher","award":["33300111"],"award-info":[{"award-number":["33300111"]}],"id":[{"id":"10.13039\/100014599","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Royal Society and Wellcome Trust","award":["204622\/Z\/16\/Z"],"award-info":[{"award-number":["204622\/Z\/16\/Z"]}]},{"DOI":"10.13039\/501100000781","name":"ERC","doi-asserted-by":"publisher","award":["ERC\u2010AdG 2016 CSI\u2010Fun, grant number 741888"],"award-info":[{"award-number":["ERC\u2010AdG 2016 CSI\u2010Fun, grant number 741888"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_12022\/1"],"award-info":[{"award-number":["MC_UU_12022\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_12022\/8"],"award-info":[{"award-number":["MC_UU_12022\/8"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>An elevated neutrophil\u2013lymphocyte 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.<\/jats:p>","DOI":"10.3390\/cancers14040963","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T22:43:22Z","timestamp":1644965002000},"page":"963","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia"],"prefix":"10.3390","volume":"14","author":[{"given":"Michele","family":"Petruzzelli","sequence":"first","affiliation":[{"name":"Medical Research Council Cancer Unit, University of Cambridge, Hutchison\/MRC Research Centre, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-975X","authenticated-orcid":false,"given":"Miriam","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Medical Research Council Cancer Unit, University of Cambridge, Hutchison\/MRC Research Centre, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK"},{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn J.","family":"Schuijs","sequence":"additional","affiliation":[{"name":"CRUK Cambridge Institute, University of Cambridge Li Ka Shing Centre, Cambridge CB2 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam O.","family":"Kleeman","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Mourikis","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Hall","sequence":"additional","affiliation":[{"name":"Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Perera","sequence":"additional","affiliation":[{"name":"Medical Research Council Cancer Unit, University of Cambridge, Hutchison\/MRC Research Centre, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shwethaa","family":"Raghunathan","sequence":"additional","affiliation":[{"name":"CRUK Cambridge Institute, University of Cambridge Li Ka Shing Centre, Cambridge CB2 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1973-224X","authenticated-orcid":false,"given":"Michele","family":"Vacca","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8523-7792","authenticated-orcid":false,"given":"Edoardo","family":"Gaude","sequence":"additional","affiliation":[{"name":"Medical Research Council Cancer Unit, University of Cambridge, Hutchison\/MRC Research Centre, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Lukey","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-1670","authenticated-orcid":false,"given":"Duncan I.","family":"Jodrell","sequence":"additional","affiliation":[{"name":"CRUK Cambridge Institute, University of Cambridge Li Ka Shing Centre, Cambridge CB2 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Frezza","sequence":"additional","affiliation":[{"name":"Medical Research Council Cancer Unit, University of Cambridge, Hutchison\/MRC Research Centre, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin F.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Laboratory Genes and Disease, Department of Laboratory Medicine Department of Dermatology, Medical University of Vienna (MUV), 1090 Vienna, Austria"},{"name":"Laboratory Genes and Disease, Department of Dermatology, Medical University of Vienna (MUV), 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok R.","family":"Venkitaraman","sequence":"additional","affiliation":[{"name":"Medical Research Council Cancer Unit, University of Cambridge, Hutchison\/MRC Research Centre, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK"},{"name":"Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore"},{"name":"Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-0023","authenticated-orcid":false,"given":"Timotheus Y. 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