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Adv."],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>\n                    Antigen heterogeneity substantially limits the efficacy of chimeric antigen receptor\u2013modified T (CAR T) cell therapy against solid tumors. Our study highlights the potent antitumor activity of low-dose decitabine-primed CAR T (dCAR T) cells in solid tumor models, a benefit previously confirmed in hematologic malignancies. Notably, dCAR T cell infusion in immunocompetent mice led to substantial elimination of mixed tumor masses containing both antigen-positive and antigen-negative cells, without the need for prior lymphodepletion. Our analysis showed notable proinflammatory remodeling of the tumor immunosuppressive microenvironment. Crucially, antigen-activated dCAR T cells sustained high levels of interferon-\u03b3 production, which induced immunogenic cell death in tumor cells and activated conventional dendritic cells. This, in turn, stimulated endogenous CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, enhancing their antigen-spreading capacity and aiding in the clearance of abscopal antigen-negative tumors. These findings reveal the robust antigen-spreading capability of dCAR T cells, underscoring their clinical potential in addressing solid tumors with inherent antigen heterogeneity.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz4088","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:53:19Z","timestamp":1778579599000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Antigen spreading mediates heterogeneous solid tumor eradication by DNA demethylating agent\u2013programmed CAR T cells"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2054-9628","authenticated-orcid":true,"given":"Yelei","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6358-0618","authenticated-orcid":true,"given":"Chuan","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8716-570X","authenticated-orcid":true,"given":"Jianshu","family":"Wei","sequence":"additional","affiliation":[{"name":"Changping Laboratory, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-9889","authenticated-orcid":true,"given":"Zhiqiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7586-5696","authenticated-orcid":true,"given":"Yuting","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2411-5390","authenticated-orcid":true,"given":"Yipeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-2820","authenticated-orcid":true,"given":"Jinhong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxia","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9352-422X","authenticated-orcid":true,"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3207-3899","authenticated-orcid":true,"given":"Weidong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"1632","article-title":"Optimized tandem CD19\/CD20 CAR-engineered T cells in refractory\/relapsed B-cell lymphoma","volume":"136","author":"Tong C.","year":"2020","unstructured":"C. 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