Persistent T cell Activation and Cytotoxicity against Glioblastoma Following Single Oncolytic Virus Treatment in a Clinical Trial

ABSTRACT: A recent first-in-human clinical trial (clinicaltrials.gov NCT03152318) demonstrated that survival in glioblastoma (GBM) patients following rQNestin34.5v.2 oncolytic virus treatment was associated with immune activation signatures. Here we provide direct in situ evidence for ongoing T cell-mediated cytotoxicity against tumor cells at late timepoints following single treatment, with deep and persistent T cell infiltration into tumor regions. Shorter distances between cleaved-caspase-3+ tumor cells and granzyme-B+ T cells were associated with longer progression-free survival following treatment. Residual viral remnants were restricted to necrotic regions, while T cells infiltrated deeply into live tumor regions. Pre-existing tumor-infiltrating T cells expanded locally following treatment, and their expansion correlated with longer overall patient survival. T cells with an early activation program closely interacted with tumor cells and were strongly enriched following treatment. These data demonstrate that single oncolytic virus treatment can expand pre-existing T cell clones and trigger persistent T cell-mediated immunity against GBM.

SUBMITTER:  

PROVIDER: S-BIAD1921 | bioimages |

REPOSITORIES: bioimages