Loss of RPN1 promotes antitumor immunity via PD-L1 checkpoint blockade in triple-negative breast cancer – experimental studies

作者：Mengxue Wang, Xunjia Li, Yushen Wu, Long Wang, Xue Zhang, Meng Dai, Yang Long, Deyu Zuo, Shengwei Li, Xuedong Yin · 发表于：International Journal of Surgery · 年份：2024 · DOI：10.1097/js9.0000000000002164 · 被引用次数：8 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、interferon and immune responses

BACKGROUND: RPN1, also known as ribophorin I (RPN1), is a type I transmembrane protein that plays an important role in glycosylation. However, the effects of RPN1 on cancer progression and immune evasion in breast cancer (BC) have not been identified. MATERIALS AND METHODS: The expression of RPN1 was evaluated using RT-qPCR and immunohistochemistry (IHC). The effects of RPN1 on tumor cells were assessed using RT-qPCR, western blotting, flow cytometry, Cell Counting Kit 8 (CCK-8), colony formation assays, and in vivo experiments. The mechanism by which RPN1 modifies programmed death ligand-1 (PD-L1) and the tumor microenvironment was examined by RT-qPCR, western blotting, co-immunoprecipitation (Co-IP), and flow cytometry. The influence of the transcription factor YY1 on RPN1 expression was revealed using bioinformatics analysis, RT-qPCR, and dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RESULTS: RPN1 is aberrantly expressed in triple-negative breast cancer (TNBC) cells, correlating with increased proliferation and poor prognosis. RPN1 mediates the post-translational modification of PD-L1, enhancing its glycosylation and stability, thus facilitating PD-L1-mediated immune escape and tumor growth. The deletion of RPN1 improves the TNBC microenvironment and enhances the efficacy of anti-PD-1 therapy. Additionally, we uncovered a novel regulatory axis involving YY1/RPN1/YBX1 in PD-L1 regulation, affecting TNBC growth and metastasis. CONCLUSIONS: Our pre...