NPM1 upregulates the transcription of PD-L1 and suppresses T cell activity in triple-negative breast cancer

Ge Qin, Xin Wang, Shubiao Ye, Yizhuo Li, Miao Chen, Shusen Wang, Tao Qin, Changlin Zhang, Yixin Li, Qian Long, Huabin Hu, Dingbo Shi, Jiaping Li, Kai Zhang, Qinglian Zhai, Yanlai Tang, Tiebang Kang, Ping Lan, Fangyun Xie, Jianjun Lu and Wuguo Deng ()
Additional contact information
Ge Qin: Collaborative Innovation Center of Cancer Medicine
Xin Wang: Collaborative Innovation Center of Cancer Medicine
Shubiao Ye: Sun Yat-sen University
Yizhuo Li: Collaborative Innovation Center of Cancer Medicine
Miao Chen: Collaborative Innovation Center of Cancer Medicine
Shusen Wang: Collaborative Innovation Center of Cancer Medicine
Tao Qin: Sun Yat-sen University
Changlin Zhang: Collaborative Innovation Center of Cancer Medicine
Yixin Li: Collaborative Innovation Center of Cancer Medicine
Qian Long: Collaborative Innovation Center of Cancer Medicine
Huabin Hu: Sun Yat-sen University
Dingbo Shi: Collaborative Innovation Center of Cancer Medicine
Jiaping Li: Collaborative Innovation Center of Cancer Medicine
Kai Zhang: Collaborative Innovation Center of Cancer Medicine
Qinglian Zhai: Collaborative Innovation Center of Cancer Medicine
Yanlai Tang: Sun Yat-sen University
Tiebang Kang: Collaborative Innovation Center of Cancer Medicine
Ping Lan: Sun Yat-sen University
Fangyun Xie: Collaborative Innovation Center of Cancer Medicine
Jianjun Lu: Sun Yat-sen University
Wuguo Deng: Collaborative Innovation Center of Cancer Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15364-z

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