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Adv."],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:p>\n                    Immunosuppressive tumor-associated macrophages (TAMs) create a barrier to effective antitumor immunity and promote therapeutic resistance. Reeducating TAMs to enhance their antitumor capabilities through phenotypic remodeling remains challenging. Here, we report a modular oncolytic herpesvirus platform, engineered with a PD-L1\u2013specific chimeric receptor integrated into the viral envelope protein (CAR-oHSV). This design endows the virus with dual tropism, enabling it to target both tumor cells and TAMs within the tumor microenvironment. In virus-resistant tumor models, CAR-oHSV preferentially targets PD-L1\n                    <jats:sup>+<\/jats:sup>\n                    TAMs and triggers a STING-dependent reprogramming into a CXCL9\n                    <jats:sup>+<\/jats:sup>\n                    phenotype, enhancing their tumor antigen cross-presentation capability and inducing an endogenous antitumor T cell response. Furthermore, this platform can synergize with adoptive T cell therapy and immune checkpoint blockade therapy to overcome immunotherapy resistance. Collectively, our findings define a precision-oncolytic platform that dismantles TAM-mediated immunosuppression while amplifying adaptive immunity, offering a promising translational avenue for cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef6767","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:04:04Z","timestamp":1789754644000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5284-4533","authenticated-orcid":true,"given":"Chaolong","family":"Lin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Vaccines for Infectious Diseases, Department of Laboratory Medicine, School of Public Health, Xiamen University, 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