Reprogramming the Immunosuppressive Microenvironment in Glioblastoma Through Oncolytic Herpes Simplex Virus Therapy:...

Area of Science:

• Neuro-oncology
• Immunotherapy
• Virology

Background:

• Glioblastoma (GBM) presents a highly immunosuppressive tumor microenvironment, hindering treatment efficacy.
• Oncolytic herpes simplex virus (oHSV) offers a dual approach of tumor-selective infection and immune modulation.

Purpose of the Study:

• To systematically review and synthesize evidence on how oHSV therapy modifies the immunosuppressive microenvironment in GBM.
• To evaluate the immunological and microenvironmental effects of oHSV-based therapies in GBM.

Main Methods:

• Systematic literature search of PubMed and Embase (2016-2025).
• Inclusion of preclinical and clinical studies investigating immunological/microenvironmental effects of oHSV in GBM.
• Qualitative narrative synthesis due to study heterogeneity.

Main Results:

• Twenty-two studies met inclusion criteria, predominantly preclinical models with limited clinical data.
• oHSV therapy promoted inflammatory signaling, antigen presentation, and T-cell recruitment.
• Counter-regulatory mechanisms like myeloid suppression and stromal barriers were also observed.

Conclusions:

• oHSV therapy demonstrates potential for glioblastoma immune microenvironment reprogramming.
• Therapeutic efficacy is linked to microenvironment remodeling, not solely viral replication.
• Further prospective clinical studies are needed to establish clinical significance and durability.