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.

作为一种有前途的局部肿瘤治疗方法，纳秒脉冲电场（nsPEF）消融引起有效的抗肿瘤免疫应答。但是，nsPEF介导的抗肿瘤免疫反应的机制及其对肿瘤微环境的影响仍不清楚。在这里，我们证明了nsPEF处理可提高肝癌细胞中PD-L1膜的水平。此外，nsPEF诱导了与PD-L1相关的细胞外囊泡的释放，导致CD8 ⁺ T细胞功能异常，可能被PD-L1阻断所逆转。生物学和功能分析还表明，nsPEF治疗会导致体内肿瘤组织中PD-L1水平升高和CD8 ⁺ T细胞浸润功能障碍，表明nsPEF治疗具有长期抗肿瘤功效。nsPEF治疗和PD-L1阻滞剂的组合可有效抑制肿瘤生长并提高荷瘤小鼠的存活率。总之，nsPEF治疗可诱导PD-L1的移位和释放，并导致浸润的CD8 ⁺ T细胞功能障碍，从而导致肿瘤在后期发展。nsPEF治疗和PD-L1阻滞剂的结合是一种有前途的肝癌治疗策略。