Blocking exposed PD-L1 elicited by nanosecond pulsed electric field reverses dysfunction of CD8+ T cells in liver cancer.

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 Lett

journal_title

Cancer letters

authors

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 S

doi

10.1016/j.canlet.2020.09.015

subject

Has Abstract

pub_date

2020-12-28 00:00:00

pages

1-11

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(20)30476-6

journal_volume

495

pub_type

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