{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:25:39Z","timestamp":1787124339115,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"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":["82272625"],"award-info":[{"award-number":["82272625"]}],"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":["82573893"],"award-info":[{"award-number":["82573893"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) is refractory to immunotherapy due to its immunologically cold microenvironment and the scarcity of mutation\u2010derived neoantigens. Here, we introduce NeoAPP, a computational tool designed to systematically decode neoantigens arising from tumor\u2010specific transcripts (TSTs) generated by transcriptional dysregulation. By integrating multi\u2010cohort transcriptomic data from 413 PDAC samples, NeoAPP identified a median of 351 neoantigens per sample, originating from 56 neoantigen\u2010encoding TSTs (neoTSTs), exceeding mutation\u2010derived neoantigens in both abundance and patient coverage. Mechanistic analyses show that noncanonical splicing junctions and transposable element activation drive neoantigen generation, while alternative promoter usage regulated by FOXA2 constitutes a potential major source of neoTSTs. In addition, a subset of neoTSTs was detectable in plasma\u2010derived extracellular vesicles and was associated with patient survival, suggesting their potential as minimally invasive biomarkers. Vaccination with neoTSTs induced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses in HLA\u2010A*02:01 and HLA\u2010A*11:01 transgenic mice and suppressed tumor growth in syngeneic PDAC models. Collectively, this work establishes TST\u2010derived neoantigens as a dominant and therapeutically actionable antigen reservoir in PDAC, advancing a transcriptome\u2010guided framework for neoantigen discovery with potential to overcome immune resistance in low\u2010mutation cancers.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70890","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:43:34Z","timestamp":1785404614000},"source":"Crossref","is-referenced-by-count":0,"title":["Harnessing Tumor\u2010Specific Transcript Diversity Uncovers a Shared Neoantigen Reservoir for Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1002","volume":"7","author":[{"given":"Jingjing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Integrative Oncology Fudan University Shanghai Cancer Center and Shanghai Key Laboratory of Medical Epigenetics Institutes of Biomedical Sciences Fudan University  Shanghai China"},{"name":"Department of 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