{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:11:57Z","timestamp":1790327517255,"version":"4.1.0"},"reference-count":98,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most lethal human malignancies, with the vast majority of patients ineligible for immunotherapy. Tumour\u2010associated macrophages (TAMs) are key regulators of the PDAC tumour microenvironment (TME), yet their transcriptional and epigenomic heterogeneity in the context of chemotherapy response is poorly understood. Therefore, we performed an exploratory single nucleus multiomics analysis of PDAC tumors stratified by histopathologic response to neoadjuvant chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Surgical resection specimens from PDAC patients were classified as responders or non\u2010responders using the American College of Pathologists (CAP) histopathologic criteria. Frozen tissue underwent simultaneous snRNA\u2010seq and snATAC\u2010seq on the 10x Genomics Chromium Single Cell Multiome platform, followed by downstream analyses such as differential gene expression, GO and hallmark pathway enrichment, pseudotime trajectory inference and ChromVAR transcription factor motif analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Multiomics profiling of 30\u00a0840 high\u2010quality nuclei revealed a myeloid compartment that differed in composition and transcriptional state between CAP\u2010defined responders and non\u2010responders in this small cohort. We observed a trend toward higher LAM\u2010like state proportions in the responders than non\u2010responders (38.4%\u00a0vs. 26.7%), although this disparity did not achieve statistical significance. The transcriptional programs of the responder myeloid cells are associated with phagocytosis and lipid handling. Chromatin accessibility analysis further suggested candidate response\u2010associated transcription factor motif accessibility patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Neoadjuvant\u2010treated PDAC tumours from CAP\u2010defined responders in this cohort myeloid landscape with apparent enrichment of LAM\u2010like states and immune\u2010activating transcriptional\/epigenetic programs. However, these findings are preliminary and hypothesis\u2010generating because of the small cohort size, heterogeneous treatment regimens, absence of matched pre\u2010treatment biopsies, and lack of knockout validation. Larger treatment cohorts and functional\/mechanistic studies are needed to determine whether LAM\u2010like myeloid programs contribute to chemotherapy response or reflect a consequence of chemotherapy treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70810","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:01Z","timestamp":1789430401000},"source":"Crossref","is-referenced-by-count":0,"title":["Exploratory single\u2010nucleus multiomics analysis of myeloid cell states associated with neoadjuvant chemotherapy response in pancreatic ductal adenocarcinoma"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2185-1301","authenticated-orcid":false,"given":"Mercy","family":"Ojetunde","sequence":"first","affiliation":[{"name":"Department of Microbiology Immunology and Cell Biology West Virginia University School of Medicine  Morgantown West Virginia 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