The following is a summary of “Tailoring vascular phenotype through AAV therapy promotes anti-tumor immunity in glioma,” published in the July 2023 issue of the Cancer Cell by Ramachandran et al.

Glioblastomas are aggressive brain tumors that are generally resistant to immunotherapy. This is related to immunosuppression and dysfunctional tumor vasculature, which inhibit T-cell infiltration. High endothelial venules (HEVs) and tertiary lymphoid structures (TLS) can be induced by LIGHT/TNFSF14, suggesting that its therapeutic expression could promote T-cell recruitment. 

Researchers use an adeno-associated viral (AAV) vector that targets brain endothelial cells to express LIGHT in the glioma vasculature (AAV-LIGHT). They discovered that a systemic AAV-LIGHT treatment induces tumor-associated HEVs and T-cell-rich TLS, extending survival in PD-1-resistant murine glioma. TCF1+CD8+ stem-like T cells, which reside in TLS and intratumoral antigen-presenting niches, are promoted by AAV-LIGHT therapy, which reduces T cell exhaustion. 

Tumor regression in response to AAV-LIGHT therapy correlates with cytotoxic/memory T-cell tumor-specific responses. Their research demonstrates that modifying the vascular phenotype via vessel-specific LIGHT expression enhances anti-tumour T-cell responses and prolongs glioma survival. These findings have implications for the treatment of other malignancies resistant to immunotherapy.

Source: sciencedirect.com/science/article/pii/S1535610823001368