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CD28 and PD-1 ICDs also undergo condensation directly, revealing a dynamic and compositionally heterogeneous signaling system. Guided by this competitive condensation mechanism, we engineer CD28 ICD mutants that preserve Lck condensation while resisting PD-1-mediated disruption. Incorporation of these condensation-selective mutants into Chimeric antigen receptor (CAR) constructs confers resistance to inhibitory signaling and enhances antitumor efficacy in vivo. These findings establish condensation as a central organizing principle of CD28 costimulation and provide a biophysical framework for engineering more resilient therapeutic T cells.<\/jats:p>","DOI":"10.1073\/pnas.2612742123","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:44:30Z","timestamp":1792601070000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["CD28 costimulation is organized by signaling condensates and counteracted by PD-1"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1642-621X","authenticated-orcid":false,"given":"Hui","family":"Chen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034t30j35","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences","place":["Beijing, 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