%0 Journal Article
%T Vimentin, inversely correlating with infiltration of CD8 + T lymphocytes, promotes nuclear translocation of PD-L1 in esophageal squamous cell carcinoma.
%A Liang Y
%A He S
%A Liu Q
%A Liu T
%A Tan Y
%A Peng T
%A Huang C
%A Lu X
%A Zheng S
%J Biochim Biophys Acta Mol Cell Res
%V 1871
%N 7
%D 2024 Jun 18
%M 38901494
%F 5.011
%R 10.1016/j.bbamcr.2024.119781
%X 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.