{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:59:09Z","timestamp":1772164749136,"version":"3.50.1"},"reference-count":30,"publisher":"American Association for Cancer Research (AACR)","issue":"9","funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["CA200681"],"award-info":[{"award-number":["CA200681"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["CA151925"],"award-info":[{"award-number":["CA151925"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001227","name":"T.J. Martell Foundation","doi-asserted-by":"publisher","award":["CA068485"],"award-info":[{"award-number":["CA068485"]}],"id":[{"id":"10.13039\/100001227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The survival rate for pancreatic ductal adenocarcinoma (PDAC) remains low. More therapeutic options to treat this disease are needed, for the current standard of care is ineffective. Using an animal model of aggressive PDAC (Kras\/p48TGF\u03b2RIIKO), we discovered an effect of TGF\u03b2 signaling in regulation of G-CSF secretion in pancreatic epithelium. Elevated concentrations of G-CSF in PDAC promoted differentiation of Ly6G+ cells from progenitors, stimulated IL10 secretion from myeloid cells, and decreased T-cell proliferation via upregulation of Arg, iNOS, VEGF, IL6, and IL1b from CD11b+ cells. Deletion of csf3 in PDAC cells or use of a G-CSF\u2013blocking antibody decreased tumor growth. Anti\u2013G-CSF treatment in combination with the DNA synthesis inhibitor gemcitabine reduced tumor size, increased the number of infiltrating T cells, and decreased the number of Ly6G+ cells more effectively than gemcitabine alone. Human analysis of human datasets from The Cancer Genome Atlas and tissue microarrays correlated with observations from our mouse model experiments, especially in patients with grade 1, stage II disease. We propose that in aggressive PDAC, elevated G-CSF contributes to tumor progression through promoting increases in infiltration of neutrophil-like cells with high immunosuppressive activity. Such a mechanism provides an avenue for a neoadjuvant therapeutic approach for this devastating disease. Cancer Immunol Res; 5(9); 718\u201329. \u00a92017 AACR.<\/jats:p>","DOI":"10.1158\/2326-6066.cir-16-0311","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T20:20:19Z","timestamp":1501791619000},"page":"718-729","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Development of Aggressive Pancreatic Ductal Adenocarcinomas Depends on Granulocyte Colony Stimulating Factor Secretion in Carcinoma Cells"],"prefix":"10.1158","volume":"5","author":[{"given":"Michael W.","family":"Pickup","sequence":"first","affiliation":[{"name":"1Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco (UCSF), San Francisco, California."}]},{"given":"Philip","family":"Owens","sequence":"additional","affiliation":[{"name":"2Department of Cancer Biology and the Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, Tennessee."}]},{"given":"Agnieszka E.","family":"Gorska","sequence":"additional","affiliation":[{"name":"2Department of Cancer Biology and the Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, Tennessee."}]},{"given":"Anna","family":"Chytil","sequence":"additional","affiliation":[{"name":"2Department of Cancer Biology and the Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, Tennessee."}]},{"given":"Fei","family":"Ye","sequence":"additional","affiliation":[{"name":"3Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University, Nashville, Tennessee."}]},{"given":"Chanjuan","family":"Shi","sequence":"additional","affiliation":[{"name":"4Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee."}]},{"given":"Valerie M.","family":"Weaver","sequence":"additional","affiliation":[{"name":"1Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of 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