髓质型胶质母细胞瘤（mGBM）具有严密的血管内皮，能够抵抗抗肿瘤免疫治疗。本研究旨在探讨肿瘤血管化与免疫逃避之间的机制联系。通过对GBM转录数据集的临床数据分析发现，髓质标志物YKL-40（CHI3L1）和Vimentin的表达与PD-L1的高表达及恶性疾病的生存率低下相关。有趣的是，PD-L1的表达主要位于血管内皮细胞中。我们在小鼠体内用高表达YKL-40梭状胶质瘤细胞GL261进行原位移植实验，结果发现增加了血管生成，减少了CD8+T细胞的浸润，导致小鼠存活率降低。在体外实验中，重组YKL-40蛋白的作用可诱导内皮细胞中PD-L1和VE-cadherin（VE-cad）的表达，同时使β-catenin/LEF向细胞核转位，其中LEF上调PD-L1的表达。YKL-40促进了VE-cad与PD-L1的解离，使PD-L1能够与来自CD8+阳性TALL-104淋巴细胞的PD-1相互作用并抑制TALL-104细胞的细胞毒性。YKL-40通过CCR5依赖的趋化作用促进了TALL-104细胞对内皮细胞的迁移和黏附，却阻碍了其反对血管的免疫作用。VE-cad或PD-L1基因敲除可消除YKL-40的效应，并恢复TALL-104细胞对血管的免疫力。综上所述，本研究揭示了一种新型的血管免疫逃逸机制，即mGBM促进肿瘤血管化和恶性转化。

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-cadherin (VE-cad) expression in endothelial cells and drove VE-cad-mediated nuclear translocation of β-catenin/LEF, where LEF upregulated PD-L1 expression. YKL-40 stimulated the dissociation of VE-cad from PD-L1, rendering PD-L1 available to interact with PD-1 from CD8+-positive TALL-104 lymphocytes and inhibit TALL-104 cytotoxicity. YKL-40 promoted TALL-104 cell migration and adhesion to endothelial cells via CCR5-dependent chemotaxis but blocked its anti-vascular immunity. Knockdown of VE-cad or the PD-L1 gene ablated the effects of YKL-40 and reinvigorated TALL-104 cell immunity against vessels. In summary, our study demonstrates a novel vascular immune escape mechanism by which mGBM promotes tumor vascularization and malignant transformation.