1. Blocking exposed PD-L1 elicited by nanosecond pulsed electric field reverses dysfunction of CD8+ T cells in liver cancer.
- Author
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Qian, Junjie, Chen, Tianchi, Wu, Qinchuan, Zhou, Lin, Zhou, Wuhua, Wu, Liming, Wang, Shuai, Lu, Jiahua, Wang, Wenchao, Li, Dazhi, Xie, Haiyang, Su, Rong, Guo, Danjing, Liu, Zhen, He, Ning, Yin, Shengyong, and Zheng, Shusen
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PROGRAMMED death-ligand 1 , *LIVER cells , *LIVER cancer , *T cells , *ELECTRIC fields - Abstract
As a promising method for local tumor treatment, nanosecond pulsed electric field (nsPEF) ablation elicits a potent anti-tumor immune response. However, the mechanism of the nsPEF-mediated anti-tumor immune response and its effects on the tumor microenvironment remains unclear. Here, we demonstrated that nsPEF treatment increased the level of membrane PD-L1 in liver cancer cells. Furthermore, nsPEF induced the release of PD-L1-associated extra-cellular vesicles, leading to the dysfunction of CD8+ T cells, which could potentially be reversed by PD-L1 blockade. Biological and functional assays also demonstrated that nsPEF treatment resulted in the increased PD-L1 level and dysfunction of infiltrated CD8+ T cells in tumor tissues in vivo, indicating the long term antitumor efficacy of nsPEF treatment. A combination of nsPEF treatment and PD-L1 blockade effectively inhibited tumor growth and improved the survival of the tumor-bearing mouse. In conclusion, nsPEF treatment induced the translocation and release of PD-L1 and contributed to the dysfunction of infiltrated CD8+ T cells, resulting in tumor progression at later stages. The combination of nsPEF treatment and PD-L1 blockade is a promising therapeutic strategy for liver cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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