Abstract：
Vimentin has been considered a canonical marker of epithelial-mesenchymal transition (EMT) and is associated with tumor escape characterized by aberrant PD-L1 expression. However, whether there is a relationship between vimentin and PD-L1 in esophageal squamous cell carcinoma (ESCC) remains poorly understood. The immunological involvement of vimentin in ESCC was first analyzed by multiplex immunofluorescence staining in ESCC tissue microarray followed by a xenografted mouse model. In vivo, C57BL/6 mice were subcutaneously transplanted with AKR cells after stable silencing of vimentin. In vivo results showed that in addition to PD-L1 and PD-L2 expression, vimentin expression was inversely correlated with CD8+ T-cell infiltration. Mechanistically, vimentin can directly interact with PD-L1 and promote nuclear translocation of PD-L1 in AKR cells. In addition, SEMA6C, STC-2 and TRAILR2 were identified as cytokines modulated by vimentin. Blockade of STC-2 and TRAILR2 in co-culture with their own primary antibodies was shown to recruit more CD8+ T cells than controls. Together, these data strongly suggest targeting Vimenin to overcome the immune cycle in ESCC.
摘要：
波形蛋白被认为是上皮-间质转化（EMT）的典型标志物，并且与以异常PD-L1表达为特征的肿瘤逃逸有关。然而,在食管鳞状细胞癌(ESCC)中,波形蛋白和PD-L1之间是否存在相关关系尚不清楚.首先通过ESCC组织微阵列中的多重免疫荧光染色，然后是异种移植小鼠模型，分析了波形蛋白在ESCC中的免疫学参与。在体内,在波形蛋白稳定沉默后，C57BL/6小鼠皮下移植AKR细胞。体内结果显示,除了PD-L1和PD-L2的表达,波形蛋白表达与CD8+T细胞浸润呈负相关。机械上,波形蛋白可直接与PD-L1相互作用，促进PD-L1在AKR细胞中的核转位。此外,SEMA6C,STC-2和TRAILR2被鉴定为由波形蛋白调节的细胞因子。与对照相比,STC-2和TRAILR2在与它们自己的初级抗体共培养中的阻断显示募集更多的CD8+T细胞。一起,这些数据强烈表明靶向Vimenin可以克服ESCC中的免疫循环.
