Oncolytic virus-mediated immunomodulation in glioblastoma: Insights from clinical trials and challenges

The pivotal involvement of the host immune system in cancer therapy has dramatically reshaped therapeutic paradigms, inaugurating the era of immunotherapy. Nonetheless, antigen-specific immunotherapies encounter substantial hurdles within the highly immunosuppressive microenvironment of glioblastoma (GBM), which thwarts antitumor T-cell immunity. Oncolytic viruses (OVs), a form of immunotherapy that inflames the GBM microenvironment, have been subject to clinical evaluation, yielding promising outcomes. Evidence increasingly indicates that OVs can modify the GBM microenvironment from an immunosuppressive to an immune active state, facilitating enhanced antitumor responses. Clinical trials demonstrate that oncolytic virotherapy is generally well-tolerated, generating data about its immune-activating effects. "Window of opportunity" trials provide insights into viral replication, pre-existing immunity, and delivery methods. However, constraints in post-treatment sampling may impede comprehensive analyses of the virotherapy-induced biological and immunological changes. This review discusses current advancements and persistent challenges in GBM trials involving OVs.