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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Qian J,Chen T,Wu Q,Zhou L,Zhou W,Wu L,Wang S,Lu J,Wang W,Li D,Xie H,Su R,Guo D,Liu Z,He N,Yin S,Zheng Sdoi
10.1016/j.canlet.2020.09.015subject
Has Abstractpub_date
2020-12-28 00:00:00pages
1-11eissn
0304-3835issn
1872-7980pii
S0304-3835(20)30476-6journal_volume
495pub_type
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