{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:30:47Z","timestamp":1773333047062,"version":"3.50.1"},"posted":{"date-parts":[[2023,6,5]]},"group-title":"Cancer Biology","reference-count":51,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec id=\"s21\">\n                  <jats:title>Background\/Aims<\/jats:title>\n                  <jats:p>Eosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s22\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Eosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient (\u0394dblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 (\n                    <jats:italic>\n                      Ccl11\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    ). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s23\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Activated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cell\n                    <jats:italic>Ccl11<\/jats:italic>\n                    expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models (\n                    <jats:italic>\n                      Ccl11\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice, \u0394dblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer.\n                    <jats:italic>In vitro<\/jats:italic>\n                    co-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. \u0394dblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s24\">\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Eosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.06.01.543287","type":"posted-content","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T10:25:20Z","timestamp":1685960720000},"source":"Crossref","is-referenced-by-count":1,"title":["Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-0319","authenticated-orcid":false,"given":"Justin","family":"Jacobse","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaryab","family":"Aziz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmine","family":"Chaparro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5385-3232","authenticated-orcid":false,"given":"Jennifer M.","family":"Pilat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Kwag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1824-6266","authenticated-orcid":false,"given":"Matthew","family":"Buendia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mae","family":"Wimbiscus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1431-5831","authenticated-orcid":false,"given":"Motomi","family":"Nasu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-8440","authenticated-orcid":false,"given":"Tsuyoshi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-3732","authenticated-orcid":false,"given":"Shinji","family":"Mine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8263-7069","authenticated-orcid":false,"given":"Hajime","family":"Orita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Revetta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-7370","authenticated-orcid":false,"given":"Sarah P.","family":"Short","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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