GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE272nnn/GSE272424/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272424GEOGSEfalseRejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophagesImmunosuppressive 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–specific 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⁺ TAMs and triggers a STING-dependent reprogramming into a CXCL9⁺ 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.2026/08/07GSE272424GSM8401836GSM8401835GSM8401838GSM8401837GSM8401840GSM840183930215272424Mus musculus