Vascular Immune Evasion of Mesenchymal Glioblastoma Is Mediated by Interaction and Regulation of VE-Cadherin on PD-L1.

ABSTRACT: The mesenchymal subtype of glioblastoma (mGBM), which is characterized by rigorous vasculature, resists anti-tumor immune therapy. Here, we investigated the mechanistic link between tumor vascularization and the evasion of immune surveillance. Clinical datasets with GBM transcripts showed that the expression of the mesenchymal markers YKL-40 (CHI3L1) and Vimentin is correlated with elevated expression of PD-L1 and poor disease survival. Interestingly, the expression of PD-L1 was predominantly found in vascular endothelial cells. Orthotopic transplantation of glioma cells GL261 over-expressing YKL-40 in mice showed increased angiogenesis and decreased CD8+ T cell infiltration, resulting in a reduction in mouse survival. The exposure of recombinant YKL-40 protein induced PD-L1 and VE-cadheri

SUBMITTER: Luo J 

PROVIDER: S-EPMC10486786 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature