GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301461/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301461GEOGSEfalseIDH1-R132H Enhances Oncolytic HSV-1 Therapy by Facilitating Viral Entry and Immune Activation in GliomaOncolytic virotherapy represents a promising yet under-explored approach for precision cancer treatment, particularly when tailored to tumor-specific molecular profiles. Patients with high-grade isocitrate dehydrogenase (IDH) mutant astrocytomas have limited treatment options and experience poor prognoses. Here, we investigate the therapeutic potential of rQNestin34.5v.2 (CAN-3110), an engineered oncolytic herpes simplex virus 1 (oHSV-1), in the context of IDH1-R132H-mutant high-grade diffuse gliomas. We demonstrate that the IDH1-R132H mutation increases glioma susceptibility to viral infection through upregulation of Nectin 1, the main cellular entry receptor for HSV-1 found in gliomas. Concurrently, IDH1-R132H-driven DNA hypermethylation suppresses interferon (IFN) signaling, an essential antiviral pathway, contributing to a permissive tumor microenvironment that facilitates viral replication and increases tumor cell susceptibility to virus-induced apoptosis. In immunocompetent IDH1-R132H murine glioma models, intratumoral administration of rQNestin34.5v.2 elicits robust immune activation, characterized by increased immune cell infiltration into the tumor and systemic IFN-γ release. However, elevated expression of poliovirus receptor (PVR or CD155) and the immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on tumor-infiltrating lymphocytes suggested a potential resistance mechanism to virotherapy. Combining rQNestin34.5v.2 with TIGIT blockade enhanced therapeutic efficacy and improved survival outcomes compared to monotherapy. These data show that IDH1-R132H modulates viral entry and immune evasion, identifying it as a predictive biomarker for oncolytic virotherapy response.2026/05/08GSE301461GSM9083587GSM9083586GSM9083589GSM9083588GSM9083590GSM9083592GSM9083591GSM9083594GSM9083593GSM9083596GSM9083585GSM908359516791301461Homo sapiens