{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:00:58Z","timestamp":1784775658370,"version":"3.55.0"},"reference-count":74,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8210101087"],"award-info":[{"award-number":["8210101087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573899"],"award-info":[{"award-number":["82573899"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Pseudouridine synthases (PUS) have been implicated in various cancers, yet their roles in pancreatic cancer immunity remain unclear. Through integrative multi\u2010omics analyses combining genomics, transcriptomics, and clinical datasets, we evaluated associations between PUS family genes and oncogenic features, including tumour microenvironment scores, immune infiltration, cancer stemness, and prognosis. Among them, PUS7 and PUS3 showed the strongest correlations with tumour\u2010promoting phenotypes, with high PUS7 expression in PDAC predicting poor overall survival. Functional assays revealed that PUS7 overexpression markedly enhanced PDAC cell proliferation, migration, and invasion. Transcriptomic profiling demonstrated that PUS7 promotes neutrophil extracellular traps formation, identifying it as a key regulator of NET\u2010mediated immune modulation. Single\u2010cell RNA sequencing of orthotopic mouse models showed PUS7 overexpression reduced macrophage infiltration and skewed macrophage polarization towards the M2 phenotype while suppressing M1 polarization. We found that PUS7 reshapes the PDAC immune landscape primarily by inducing NETs, which drive macrophage polarization from M1 to M2, fostering immune suppression and tumour progression. The PUS7\u2013NET\u2013M2\/M1 axis thus represents a novel mechanism of PDAC pathogenesis and a potential therapeutic target in this lethal malignancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>PUS7 enhances pancreatic ductal adenocarcinoma progression by modulating the tumour immune microenvironment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>PUS7 induces neutrophil extracellular trap formation within pancreatic tumours.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>NETs reprogram tumour\u2010associated macrophages from an M1 to an M2 phenotype, promoting immune suppression.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70581","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:04:23Z","timestamp":1767769463000},"source":"Crossref","is-referenced-by-count":2,"title":["Multi\u2010omics analysis identifies PUS7 as an immune modulator driving NETs\u2010mediated macrophage polarization in pancreatic cancer"],"prefix":"10.1002","volume":"16","author":[{"given":"Jike","family":"Fang","sequence":"first","affiliation":[{"name":"Department of General Surgery Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University Guangzhou China"},{"name":"The Second School of Clinical Medicine Southern Medical University Guangzhou 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