{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301461/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301461"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"IDH1-R132H Enhances Oncolytic HSV-1 Therapy by Facilitating Viral Entry and Immune Activation in Glioma","description":"Oncolytic 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.","dates":{"publication":"2026/05/08"},"accession":"GSE301461","cross_references":{"GSM":["GSM9083587","GSM9083586","GSM9083589","GSM9083588","GSM9083590","GSM9083592","GSM9083591","GSM9083594","GSM9083593","GSM9083596","GSM9083585","GSM9083595"],"GPL":["16791"],"GSE":["301461"],"taxon":["Homo sapiens"]}}