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  • Title: NPM1 upregulates the transcription of PD-L1 and suppresses T cell activity in triple-negative breast cancer.
    Author: Qin G, Wang X, Ye S, Li Y, Chen M, Wang S, Qin T, Zhang C, Li Y, Long Q, Hu H, Shi D, Li J, Zhang K, Zhai Q, Tang Y, Kang T, Lan P, Xie F, Lu J, Deng W.
    Journal: Nat Commun; 2020 Apr 03; 11(1):1669. PubMed ID: 32245950.
    Abstract:
    Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction plays a crucial role in tumor-associated immune escape. Here, we verify that triple-negative breast cancer (TNBC) has higher PD-L1 expression than other subtypes. We then discover that nucleophosmin (NPM1) binds to PD-L1 promoter specifically in TNBC cells and activates PD-L1 transcription, thus inhibiting T cell activity in vitro and in vivo. Furthermore, we demonstrate that PARP1 suppresses PD-L1 transcription through its interaction with the nucleic acid binding domain of NPM1, which is required for the binding of NPM1 at PD-L1 promoter. Consistently, the PARP1 inhibitor olaparib elevates PD-L1 expression in TNBC and exerts a better effect with anti-PD-L1 therapy. Together, our research has revealed NPM1 as a transcription regulator of PD-L1 in TNBC, which could lead to potential therapeutic strategies to enhance the efficacy of cancer immunotherapy.
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