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Here we engineer geometry\u2010programmable DNA origami that precisely encodes double\u2010stranded DNA (dsDNA) valency and spacing to promote cooperative cGAS clustering and STING activation. Systematic architectural modulation identifies an optimal configuration within tested ranges, in which 60\u2010bp dsDNA ligands arranged with \u223c16.3\u00a0nm periodicity induce approximately twofold stronger STING signaling than free dsDNA counterparts. We further integrate these origamis with the probiotic\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    Nissle 1917 via transporter\u2010mediated surface anchoring, forming a living immunomaterial interface for localized ligand presentation in colorectal tumors. In microsatellite\u2010stable colorectal cancer models, this biohybrid system drives robust intratumoral STING activation, promotes T\u2010cell\u2010inflamed immune remodeling, and suppresses tumor growth by \u223c83.5% relative to controls. This work establishes a geometry\u2010programmable living immunomaterial translating nanoscale architectural design into spatially confined innate immune signaling.\n                  <\/jats:p>","DOI":"10.1002\/adma.74187","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:36:50Z","timestamp":1784536610000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Geometry\u2010Programmable Living Immunomaterials for Spatial Control of Innate Immune Signaling"],"prefix":"10.1002","volume":"38","author":[{"given":"Haoyuan","family":"Xu","sequence":"first","affiliation":[{"name":"Microbial Sensing and Imaging Analysis Laboratory Institute of Functional Nano &amp; Soft Materials &amp; Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO\u2010CIC) Soochow University  Suzhou Jiangsu P. R. 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