By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity.
The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor types, including glioblastoma (GBM), the most common and lethal form of adult brain cancer.
TNFα-blocking antibodies and macrophages derived from <i>Bai1<sup>-/-</sup></i> mice were used.<b>Results:</b> RAMBO treatment of mice reduced recruitment and activation of macrophages/microglia in mice with brain tumors, and showed increased virus replication compared with rHSVQ1.
Interestingly, a significant effect of the brain tumor microenvironment on Treg lineage programming was observed, based on higher levels of brain tumor-resident Tregs expressing glucocorticoid-induced tumor necrosis factor receptor and CD103 and lower levels of Tregs expressing CD62L and CD45RB compared with peripheral Tregs.
These results suggest that TNF-alpha could modulate HIV and brain tumor pathogenesis and immune-mediated inflammation in the central nervous system (CNS) by regulation of CXCR4 expression.
Detection of tumor necrosis factor-alpha protein and messenger RNA in human glial brain tumors: comparison of immunohistochemistry with in situ hybridization using molecular probes.
To obtain an insight into the network of cytokine gene transcription in the brain tumour microenvironment, we investigated the expression of genes encoding for interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta 1, -beta 2 and -beta 3 in freshly excised brain tumour samples and autologous peripheral blood mononuclear cells.