{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:40:21Z","timestamp":1789400421010,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We previously reported that an increased M1\/M2 ratio and decreased PDL1+ M2- like tumor-associated macrophages (TAM) are associated with longer survival in patients with pancreatic adenocarcinoma (PDA). Targeting M2-like macrophages may improve patients\u2019 outcomes. In this pilot study, we hypothesized targeting M2-like macrophages, regulated by the colony stimulating factor-1 (CSF1) pathway, would be safe and induce an intratumoral immune response in patients with PDA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested perioperative combination immunotherapy (CI) with GM-CSF-secreting allogenic pancreatic tumor cell vaccine (GVAX)\/cyclophosphamide (CY), pembrolizumab (Pem), and CSF1 receptor blockade (IMC-CS4) in patients with PDA. Patients received two neoadjuvant cycles of CI followed by surgery and four adjuvant cycles of CI. Subsequently, they received a booster Pem every 3 weeks and GVAX\/CY every 6 months, for up to one year. The co-primary endpoints were safety and immune response in paired biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine patients were enrolled and treated in this study. We observed two immune related grade 3\/4 AEs (diarrhea and rash). Comparison of paired biopsies showed five of eight evaluable patients met the immunologic endpoint with &amp;gt;80% increase in CD8+ T cells. The increase was at least 1.8 times the baseline median absolute deviation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CI has a manageable safety profile and leads to increased intratumoral cytotoxic effector T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT03153410<\/jats:ext-link>\n                      , identifier NCT03153410\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1715761","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:47:07Z","timestamp":1773038827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Safety and immunologic impact of neoadjuvant\/adjuvant GVAX, cyclophosphamide, pembrolizumab, and anti-CSF1R agent IMC-CS4 in pancreatic adenocarcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Arielle","family":"Urman","sequence":"first","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Ding","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School 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