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However, the interfere of mature immune checkpoints encounter efficacy challenges in solid tumors, which underlies a critical barrier in clinical translation of multiple potential targets. Herein, we propose a biochemical immune modulation strategy for immunosuppression reversal by blocking the mature of CD47 within the endoplasmic reticulum (ER). Clinically used radionuclides iodine\u2010131 (\n                    <jats:sup>131<\/jats:sup>\n                    I) is reengineered to encapsulate within microporous barium titanate nanoparticles, forming an immunoactive nanomodulator. Leveraging polarized and collisional relaxation, the electrons emitted from\n                    <jats:sup>131<\/jats:sup>\n                    I mediate continuous disulfide bond reduction, blocking CD47 folding and surface translocation, resulting in a 93.6% reduction in CD47 expression. Together with the remarkable increase of tumor antigen presentation induced by ER reductive stress in pancreatic tumor\u2010bearing mice, we realize a 93% tumor inhibition and a 3\u2010fold prolongation of survival. This work underscores the role of organellar biochemistry in reshaping immunosuppression for tumor immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202517261","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:21:53Z","timestamp":1776835313000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reprogramming Disulfide Reduction in Endoplasmic Reticulum Uncouples Immune Evasion of Pancreatic Cancer"],"prefix":"10.1002","volume":"38","author":[{"given":"Zhongqiu","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine The First Affiliated Hospital of Naval Medical University  Shanghai P. R. 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