{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:54:11Z","timestamp":1781535251605,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"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":["82073139"],"award-info":[{"award-number":["82073139"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Pancreatic cancer remains a highly lethal malignancy with limited therapeutic efficacy and untapped immunotherapeutic potential, largely constrained by immune cell heterogeneity in the tumour microenvironment. Tumour\u2010associated macrophages (TAMs), especially tissue\u2010resident macrophages (TRMs), exert complex regulatory roles in tumour progression. Here, we integrated single\u2010cell RNA sequencing (scRNA\u2010seq) and bulk RNA sequencing (bulk\u2010seq) data from the GEO and TCGA databases to characterize macrophage heterogeneity and its functional impacts in pancreatic cancer. We delineated the tumour microenvironment landscape and identified a specific TRM subpopulation. Cell communication analysis revealed extensive interactions between TRMs and other cell types, including CXCL\/MIF and notably upregulated SPP1 signalling in tumour tissues. We further established a TAM scoring system and found that clusters 4, 5, 9 and 10 were significantly associated with patient survival. Among them, TRM cluster 4 showed the highest predictive efficacy for 5\u2010year and 10\u2010year mortality, and effectively stratified patients into high\u2010 and low\u2010risk groups with distinct differences in survival, immune cell infiltration and immune checkpoint expression. Importantly, TRM_C4 scores exhibited significant changes after immunotherapy, with decreased scores in responders and increased scores in non\u2010responders. Together, our findings demonstrate the critical involvement of pancreatic cancer tissue\u2010resident macrophages in tumour progression and immunotherapy response, and suggest that targeting specific macrophage subpopulations may represent a novel strategy to enhance immunotherapy efficacy and improve clinical outcomes for pancreatic cancer patients.<\/jats:p>","DOI":"10.1111\/jcmm.71212","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:10:17Z","timestamp":1780027817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell RNA\u2010Seq Combined With Bulk RNA\u2010Seq Revealed the Involvement of Pancreatic Cancer Tissue\u2010Resident Macrophages in Tumour Progression and the Immunotherapy Response"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8447-0666","authenticated-orcid":false,"given":"Bin","family":"Wu","sequence":"first","affiliation":[{"name":"The Graduate School of Fujian Medical University  Fuzhou China"},{"name":"Department of General Surgery Fujian Medical University Union Hospital  Fuzhou China"},{"name":"Department of Hepatobiliary Surgery The Second Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chundong","family":"Hu","sequence":"additional","affiliation":[{"name":"The Graduate School of Fujian Medical University  Fuzhou China"},{"name":"Department of General Surgery Fujian Medical University Union Hospital  Fuzhou China"},{"name":"Department of Hepatobiliary Surgery The Second Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9988-7216","authenticated-orcid":false,"given":"Fengchun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Fujian Medical University Union Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21708"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32409-6"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910836"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.116392"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0479-5"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01308"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.648917"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08911-4"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0858-1"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00370"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10040960"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252510"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00347-z"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06002-x"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001601"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13340-023-00624-2"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.08.010"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.04.008"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01579-x"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00204"},{"issue":"214","key":"e_1_2_13_22_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/ddg.12290","article-title":"Macrophages\u2014Sensors and Effectors Coordinating Skin Damage and Repair","volume":"12","author":"Willenborg S.","year":"2014","journal-title":"Journal Der Deutschen Dermatologischen Gesellschaft"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2021.04.007"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200001000-00002"},{"key":"e_1_2_13_25_1","first-page":"4","article-title":"Inactivation of mTORC2 in Macrophages Is a Signature of Colorectal Cancer That Promotes Tumorigenesis. 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