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Pyroptosis has emerged as a potential strategy to overcome radioresistance, yet its regulatory mechanisms remain unclear. Using LC\u2010MS\/MS\u2010based proteomic profiling of tumor tissues from patients with GC treated with neoadjuvant chemoradiotherapy, we identified tumor\u2010intrinsic lymphotoxin beta receptor (LT\u03b2R), previously considered mainly an immune cell membrane protein, as a candidate determinant of poor radiotherapy response. Functional studies in GC cell lines, xenografts, and patient\u2010derived organoids (PDOs) showed that\n                    <jats:italic>LT\u03b2R<\/jats:italic>\n                    depletion enhanced radiosensitivity, whereas\n                    <jats:italic>LT\u03b2R<\/jats:italic>\n                    overexpression promoted radioresistance. Integrated RNA\u2010seq, Ribo\u2010seq, and polysome profiling showed that\n                    <jats:italic>LT\u03b2R<\/jats:italic>\n                    loss reduced translational efficiency of\n                    <jats:italic>SARM1<\/jats:italic>\n                    under irradiation. Mechanistically, irradiation increased LT\u03b2R stability in a glycosylation\u2010dependent manner and promoted nuclear translocation. In the nucleus, LT\u03b2R enhanced TRIM28\u2010mediated SUMOylation of PCBP2, promoting cytoplasmic redistribution of PCBP2 and increased translational efficiency of\n                    <jats:italic>SARM1<\/jats:italic>\n                    . Consistently,\n                    <jats:italic>LT\u03b2R<\/jats:italic>\n                    suppressed irradiation\u2010induced pyroptosis through the NLRP3\/caspase\u20101\/GSDMD pathway. We further identified EMD638683 as an LT\u03b2R\u2010binding compound through structure\u2010based virtual screening, and showed that cRGD\u2010modified liposomes improved its tumor\u2010targeted delivery and enhanced LT\u03b2R reduction, radiosensitization, and tumor suppression in PDO and xenograft models. Together, these findings highlight LT\u03b2R as a promising therapeutic target to improve radiotherapy efficacy in GC.\n                  <\/jats:p>","DOI":"10.1002\/advs.76157","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:38:26Z","timestamp":1782124706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Radiation\u2010Induced Tumor\u2010Intrinsic LT\u03b2R N\u2010Glycosylation Suppresses Pyroptosis Through TRIM28\u2010Mediated PCBP2 SUMOylation to Promote Gastric Cancer Radioresistance"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6051-1964","authenticated-orcid":false,"given":"Weijie","family":"Zang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery Affiliated Hospital of Nantong University Medical School of Nantong University  Nantong Jiangsu China"},{"name":"Research Center of Clinical Medicine 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