{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:36:48Z","timestamp":1788349008251,"version":"build-2803163510"},"reference-count":68,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":333,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Langerhans cells (LCs) are epithelial antigen\u2010presenting cells (APC) contributing to immune surveillance. LCs depend on interleukin 34 (IL34) production by epithelial cells. This study aimed to uncover mechanisms of alteration of IL34 and LC function in squamous cell carcinoma (SCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cancer cohort data were used to identify associations between SCC and IL34. ATAC\u2010seq of keratinocytes (KCs) and LCs from a murine model of epithelial hyperplasia, driven by HPV16 E7 oncoprotein (K14E7), was analysed. Transcriptomic data were used to validate findings. RNAscope, RT\u2010qPCR, ELISA and confocal imaging was used to analyse IL34 expression and LCs in a spatial context.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>IL34<\/jats:italic> mRNA is downregulated in human SCCs of the head and neck, the cervix, the lung and the oesophagus, and low <jats:italic>IL34<\/jats:italic> expression is associated with poor survival. We demonstrate that KCs of K14E7 mice have reduced <jats:italic>Il34<\/jats:italic> gene accessibility, mRNA and protein, as well as broad changes in promotor accessibility associated with cell adhesion and immune responses. Chromatin accessibility was substantially changed in LCs, including increased accessibility of the <jats:italic>Csf1r<\/jats:italic> gene, and changes in promotors associated with cytoskeleton arrangement and antigen processing and presentation. We discovered altered spatial LC dendrite organisation in hyperproliferative epithelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Squamous cell carcinoma of the cervix, head and neck, oesophagus and lung demonstrate downregulation of IL34, which is associated with poor survival, and with alterations in LC spatial organisation and function. These findings suggest that reduced IL34 expression in SCC may contribute to impaired local immunity through LC dysregulation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.70018","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T10:05:10Z","timestamp":1732874710000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Squamous cell carcinoma is associated with reduced IL34 expression, alterations in the Langerhans cell antigen\u2010processing\u2010presentation machinery and poor patient survival"],"prefix":"10.1002","volume":"13","author":[{"given":"Thi Viet Trinh","family":"Dang","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin R","family":"Gillinder","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane QLD Australia"},{"name":"Queensland Institute of Medical Research Berghofer  Herston QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onkar","family":"Mulay","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane QLD Australia"},{"name":"Queensland Institute of Medical Research Berghofer  Herston QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan","family":"Vo","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane QLD Australia"},{"name":"Queensland Institute of Medical Research Berghofer  Herston QLD Australia"},{"name":"School of Biomedical Sciences and Pharmacy The University of Newcastle  Callaghan NSW Australia"},{"name":"Precision Medicine Research Program Hunter Medical Research Institute  New Lambton Heights NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M","family":"Mehdi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Frazer Institute The University of Queensland  Brisbane QLD Australia"},{"name":"QCIF Bioinformatics Queensland Cyber Infrastructure Foundation Ltd  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Brooks","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham R","family":"Leggatt","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Hume","sequence":"additional","affiliation":[{"name":"Mater Research Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-4680","authenticated-orcid":false,"given":"Ian H","family":"Frazer","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4456-9480","authenticated-orcid":false,"given":"Janin","family":"Chandra","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Chapter 10 \u2013 Epithelial Pathology","author":"Neville B","year":"2019"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-007-0014-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.06.169"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103326"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2315096120"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-206-43720A"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pvr.2017.10.001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.06.011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004466"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.201"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400216"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902191"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.222"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.2100006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000156"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01768"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127155"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.03.1162"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152886"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.11.001"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545917"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2360"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1307"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-022-00577-9"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqad075"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11053-8"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000835"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24627"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01033"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1154370"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.MR1117-457R"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190290"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12282-020-01123-x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/25785826.2019.1691429"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18796-8"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-1170"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxz074"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28445"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00275"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.11.037"},{"key":"e_1_2_9_42_1","doi-asserted-by":"crossref","unstructured":"PavilionG VuH XiongZet\u00a0al.Spatial analysis of HPV associated cervical intraepithelial neoplastic tissues demonstrate distinct immune signatures associated with cervical cancer progression.bioRxiv.2024.https:\/\/doi.org\/10.1101\/2024.10.02.611623","DOI":"10.1101\/2024.10.02.611623"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-017-0424-5"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12250-021-00413-8"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2018.11"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1539"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2014.192"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.6MA0519-172R"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-1-48"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.3.1873-1881.1996"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052622"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2024.100625"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0546-8"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_9_55_1","first-page":"265","article-title":"Cell detection with star\u2010convex polygons","volume":"11071","author":"Schmidt U","year":"2018","journal-title":"Med Image Comput Comput Assist Interv"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_9_57_1","unstructured":"AndrewsS.FastQC. Available from:https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_9_61_1","unstructured":"Broad\u2010Institute.Picard. Available from:https:\/\/broadinstitute.github.io\/picard\/"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10730"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13182"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2840"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv145"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1630"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-482"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.70018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T06:31:13Z","timestamp":1735281073000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.70018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":68,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/cti2.70018"],"URL":"https:\/\/doi.org\/10.1002\/cti2.70018","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2024-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70018"}}