Persistent spatial immune responses in glioblastoma following oncolytic virus therapy

Glioblastoma (GBM) remains highly resistant to immunotherapy due to limited T-cell infiltration and a profound immunosuppressive tumor microenvironment (TME). A recent first-in-human clinical trial of the oncolytic herpes simplex virus rQNestin34.5 v.2 (NCT03152318) shows that a single intratumoral dose can trigger durable T-cell activation and sustained cytotoxic engagement within tumor tissue. Spatial profiling reveals persistent immune-tumor interactions after viral clearance that correlate with clinical outcome. These findings indicate that oncolytic virotherapy can remodel tumor-immune architecture and establish lasting spatial immune surveillance. This correspondence discusses the mechanistic and translational implications of persistent spatial T-cell immunity in GBM.