{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:38:05Z","timestamp":1785544685625,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,29]]},"group-title":"Cancer Biology","reference-count":27,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54 CA209971"],"award-info":[{"award-number":["U54 CA209971"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U01 CA264611"],"award-info":[{"award-number":["U01 CA264611"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54CA20997105"],"award-info":[{"award-number":["U54CA20997105"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5DP5OD01982205"],"award-info":[{"award-number":["5DP5OD01982205"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R01CA24063801A1"],"award-info":[{"award-number":["1R01CA24063801A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5R01AG06827902"],"award-info":[{"award-number":["5R01AG06827902"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"crossref","award":["W81XWH2110143"],"award-info":[{"award-number":["W81XWH2110143"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Bulk transcriptomic classifiers stratify pancreatic ductal adenocarcinoma (PDAC) into classical and basal-like subtypes with prognostic and therapeutic relevance, yet increasing evidence indicates that these epithelial programs frequently coexist within individual tumors. How these intermediate states affect the local tumor microenvironment remains poorly defined. Here, we integrate multiplexed ion beam imaging (MIBI) with bulk RNA sequencing to resolve epithelial subtype identity at the level of spatially contiguous cancer nests and quantify their associated microenvironments. Across 47 primary tumor samples from 34 patients, we identified classical, intermediate, and basal cancer cell states at single-cell resolution and delineated discrete cancer nests with mixed or dominant subtype compositions. Distance-resolved spatial analysis reveals that basal-rich cancer nests are surrounded by locally immunosuppressive microenvironments characterized by reduced expression of MHC class II and co-stimulatory molecules in proximal myeloid cells, independent of myeloid abundance. These regions are enriched in fibroblast-dominated neighborhoods and distinct cell-cell interaction architectures. Using EcoTyper analysis of two independent bulk RNA-seq cohorts, including an OHSU discovery cohort (N = 277 patients) and TCGA as a validation cohort (N = 147 patients), we identified poor-prognosis tumor ecotypes enriched for basal epithelial states that similarly exhibited depleted myeloid antigen presentation signatures, linking spatial niche phenotypes to transcriptional ecotypes and patient outcomes. Together, these findings demonstrate that epithelial subtype programs in PDAC are organized at the level of spatially defined cancer nests and that basal cancer programs reside within localized niches of myeloid antigen presentation dysfunction, linking intratumoral architecture to immune suppression and clinical prognosis.<\/jats:p>","DOI":"10.64898\/2026.07.28.741300","type":"posted-content","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:25:12Z","timestamp":1785335112000},"source":"Crossref","is-referenced-by-count":0,"title":["Spatially Resolved Epithelial States Delineate Immunosuppressive Niches of Impaired Myeloid Antigen Presentation in PDAC"],"prefix":"10.64898","author":[{"given":"Cameron","family":"Walker","sequence":"first","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeesha","family":"Piyadasa","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooks","family":"Benard","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Pelz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Eng","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Hawthorne","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-2413","authenticated-orcid":false,"given":"Rosalie","family":"Sears","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR"},{"name":"Brenden-Colson Center for Pancreatic Care, Knight Cancer Institute, Oregon Health & Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-9858","authenticated-orcid":false,"given":"Andrew J.","family":"Gentles","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"},{"name":"Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Risom","sequence":"additional","affiliation":[{"name":"Department of Research Pathology, Genentech, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1531-5067","authenticated-orcid":false,"given":"Michael","family":"Angelo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026073114401166000_2026.07.28.741300v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70043"},{"key":"2026073114401166000_2026.07.28.741300v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3398"},{"key":"2026073114401166000_2026.07.28.741300v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2344"},{"key":"2026073114401166000_2026.07.28.741300v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature16965"},{"key":"2026073114401166000_2026.07.28.741300v1.5","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1158\/1078-0432.CCR-19-1467","article-title":"Purity Independent Subtyping of Tumors (PurIST), a clinically robust, single sample classifier for tumor subtyping in pancreatic cancer","volume":"26","year":"2020","journal-title":"Clin Cancer Res Off J Am Assoc Cancer Res"},{"key":"2026073114401166000_2026.07.28.741300v1.6","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000363RR"},{"key":"2026073114401166000_2026.07.28.741300v1.7","doi-asserted-by":"crossref","unstructured":"Kalfakakou D , Cameron DC , Kawaler EA , Tsuda M , Wang L , Jing X , et al. 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