TCF3 activates VEGFA transcription and reinforces PD-L1 expression in lung adenocarcinoma cells via NF-κB to attenuate the cytotoxicity of CD8+ T cells

In response to the clinical dilemma of insufficient immune treatment response rate for lung adenocarcinoma (LUAD), this study aims to analyze the regulatory mechanism of the TCF3/VEGFA axis on CD8+ T cells’ function. Bioinformatics analysis predicted the upstream transcription factors of VEGFA. Dual luciferase and ChIP assays verified the binding relationship between VEGFA and TCF3. WB detected the expression of VEGFA, NF-κB-related markers and PD-L1. Flow cytometry and immunofluorescence detected the expression of PD-L1. The cytotoxicity efficiency of CD8+ T cells was evaluated in a co-cultivation system. A subcutaneous LUAD mouse model was constructed to verify the role of TCF3/VEGFA in vivo. VEGFA was transcriptionally activated by its upstream transcription factor TCF3 (p + T cell cytotoxicity (p p This article reveals that the TCF3/VEGFA axis enhances the expression of PD-L1 in LUAD by activating the NF-κB signaling pathway, thereby weakening the cytotoxicity of CD8+ T cells.