PLK1 inhibitors were shown, in vitro and in vivo, to possess inhibitory activities against non-small cell lung cancer (NSCLC), and such inhibition has been proven by clinical trials. However, it remains unclear whether and how the immune microenvironment is associated with the action. In this study, we found that inhibiting PLK1 could alter the tumor immune microenvironment by increasing DC maturation, and enriching T cells infiltration. PLK1 inhibitors, serving as immunogenic cell death (ICD) inducers, indirectly activated DCs, instead of directly acting on DC cells, through the surface expression of costimulatory molecules on and enhanced phagocytosis by DCs. Furthermore, upon targeting PLK1, tumor cells that had undergone ICD were converted into an endogenous vaccine, which triggered the immune memory responses and protected the mice from tumor challenge. Collectively, these results suggested that the PLK1 inhibitor might function as an immune modulator in antitumor treatment.

中文翻译：

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PLK1 抑制可诱导免疫原性细胞死亡并增强针对 NSCLC 的免疫力。


PLK1抑制剂在体外和体内均显示出对非小细胞肺癌（NSCLC）具有抑制活性，并且这种抑制作用已得到临床试验的证实。然而，尚不清楚免疫微环境是否以及如何与该作用相关。在这项研究中，我们发现抑制 PLK1 可以通过增加 DC 成熟和丰富 T 细胞浸润来改变肿瘤免疫微环境。 PLK1抑制剂作为免疫原性细胞死亡（ICD）诱导剂，通过在DC表面表达共刺激分子并增强DC的吞噬作用，间接激活DC，而不是直接作用于DC细胞。此外，在靶向 PLK1 后，经过 ICD 的肿瘤细胞被转化为内源性疫苗，从而触发免疫记忆反应并保护小鼠免受肿瘤攻击。总的来说，这些结果表明 PLK1 抑制剂可能在抗肿瘤治疗中充当免疫调节剂。