{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Klein L"],"funding":["Deutsche Forschungsgemeinschaft","Wilhelm Sander-Stiftung","Deutsche Forschungsgemeinschaft (German Research Foundation)","Wilhelm Sander-Stiftung (Wilhelm Sander Foundation)","Fritz Thyssen Stiftung","Deutsche Krebshilfe","Fritz Thyssen Stiftung (Fritz Thyssen Foundation)","Deutsche Krebshilfe (German Cancer Aid)"],"pagination":["335"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11704331"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity and co-existence, linked to a diverse microenvironment and worse clinical outcome. However, the underlying mechanisms remain unclear. Here, by combining preclinical models, multi-center clinical, transcriptomic, proteomic, and patient bioimaging data, we identify an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic macrophages driving subtype co-existence and an immunosuppressive microenvironment. ATAC-, ChIP-, and RNA-seq analyses reveal that JUNB/AP1- and HDAC-mediated epigenetic programs repress pro-inflammatory signatures in tumor cells, antagonizing cJUN/AP1 signaling, favoring a therapy-responsive classical neoplastic state. This dichotomous regulation"],"journal":["Nature communications"],"pubmed_title":["Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer."],"pmcid":["PMC11704331"],"funding_grant_id":["70112999","70115054","2021.159.1 and 2021.159.2","KFO5002","10.20.2.038MN; 10.23.2.021MN"],"pubmed_authors":["Penz F","Krebs N","Samuel RD","Blandau A","Kuffer S","Espinet E","Urbach L","Tu M","Klein L","Papantonis A","Vyas F","Aliar K","Hessmann E","Latif MU","Trumpp A","Grunwald BT","Kishore U","Khokha R","Ellenrieder V","Chan N","Wegwitz F","Grimm D","Wu X","Singh SK"],"additional_accession":[]},"is_claimable":false,"name":"Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer.","description":"Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity and co-existence, linked to a diverse microenvironment and worse clinical outcome. However, the underlying mechanisms remain unclear. Here, by combining preclinical models, multi-center clinical, transcriptomic, proteomic, and patient bioimaging data, we identify an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic macrophages driving subtype co-existence and an immunosuppressive microenvironment. ATAC-, ChIP-, and RNA-seq analyses reveal that JUNB/AP1- and HDAC-mediated epigenetic programs repress pro-inflammatory signatures in tumor cells, antagonizing cJUN/AP1 signaling, favoring a therapy-responsive classical neoplastic state. This dichotomous regulation","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-01T15:01:02.491Z","creation":"2026-04-08T13:34:33.297Z"},"accession":"S-EPMC11704331","cross_references":{"pubmed":["39762215"],"doi":["10.1038/s41467-024-55330-7"]}}