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We show here that the ablation of eosinophils severely compromises antitumor immunity in syngeneic and genetic models of colorectal cancer (CRC), which can be attributed to defective Th1 and CD8+ T cell responses. The specific loss of GM-CSF signaling or IRF5 expression in the eosinophil compartment phenocopies the loss of the entire lineage. GM-CSF activates IRF5 in vitro and in vivo and can be administered recombinantly to improve tumor immunity. IL-10 counterregulates IRF5 activation by GM-CSF. CRC patients whose tumors are infiltrated by large numbers of eosinophils also exhibit robust CD8 T cell infiltrates and have a better prognosis than patients with eosinophillow tumors. The combined results demonstrate a critical role of eosinophils in tumor control in CRC and introduce the GM-CSF\u2013IRF5 axis as a critical driver of the antitumor activities of this versatile cell type.<\/jats:p>","DOI":"10.1084\/jem.20190706","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T13:50:13Z","timestamp":1600955413000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":89,"title":["The GM-CSF\u2013IRF5 signaling axis in eosinophils promotes antitumor immunity through activation of type 1 T cell responses"],"prefix":"10.1084","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8679-9666","authenticated-orcid":true,"given":"Isabelle C.","family":"Arnold","sequence":"first","affiliation":[{"name":"Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland 1"},{"name":"Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"Artola-Boran","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Gurtner","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Bertram","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-3320","authenticated-orcid":true,"given":"Michael","family":"Bauer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9164-7656","authenticated-orcid":true,"given":"Ziva","family":"Frangez","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, Bern, Switzerland 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-7867","authenticated-orcid":true,"given":"Burkhard","family":"Becher","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-7140","authenticated-orcid":true,"given":"Manfred","family":"Kopf","sequence":"additional","affiliation":[{"name":"Department of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9855-4305","authenticated-orcid":true,"given":"Shida","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, Bern, Switzerland 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9404-7736","authenticated-orcid":true,"given":"Hans-Uwe","family":"Simon","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, Bern, Switzerland 3"},{"name":"Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-3819","authenticated-orcid":true,"given":"Alexandar","family":"Tzankov","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital of Basel, Basel, Switzerland 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"2023072717372286200_bib1","volume-title":"AJCC Cancer Staging Manual","author":"American Joint Committee on Cancer","year":"2002","edition":"Sixth edition"},{"key":"2023072717372286200_bib2","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1084\/jem.20172049","article-title":"Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation","volume":"215","author":"Arnold","year":"2018","journal-title":"J. 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