肝细胞癌（HCC）是一种常见的恶性肿瘤，预后较差。近年来,免疫检查点抑制剂（ICIs）在HCC患者的临床治疗中取得了突破，但HCC患者对ICIs的总体反应率仍然很低，并且没有经过验证的生物标志物可用于指导临床决策。这里,我们证明长链非编码RNALnc-CCNH-8在HCC中高表达,并与不良预后相关.功能上,升高的Lnc-CCNH-8灭活共培养的T细胞在体外和免疫活性小鼠模型中的抗肿瘤免疫力受损。机械上,上调Lnc-CCNH-8可以海绵微小RNA(miR)-217来调控PD-L1的表达。此外,Lnc-CCNH-8还可以通过miR-3173/PKP3轴稳定PD-L1。此外，携带Lnc-CCNH-8高表达肿瘤的小鼠对抗PD-L1单克隆抗体治疗具有显著的治疗敏感性。更重要的是,血浆外泌体Lnc-CCNH-8水平高的HCC患者对ICIs有更好的治疗反应。一起来看,我们的结果揭示了Lnc-CCNH-8通过以miR-217/miR-3173依赖性方式上调PD-L1来诱导CD8+T细胞介导的杀伤免疫逃逸的功能，这也揭示了肝癌中PD-L1调节的新机制，外泌体Lnc-CCNH-8可作为HCC免疫治疗反应的预测指标。
Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis. In recent years, immune checkpoint inhibitors (ICIs) have enabled breakthroughs in the clinical treatment of patients with HCC, but the overall response rate to ICIs in HCC patients is still low, and no validated biomarker is available to guide clinical decision making. Here, we demonstrated that the long non-coding RNA Lnc-CCNH-8 is highly expressed in HCC and correlates with poor prognosis. Functionally, elevated Lnc-CCNH-8 inactivated co-cultured T cells in vitro and compromised antitumor immunity in an immunocompetent mouse model. Mechanistically, up-regulated Lnc-CCNH-8 can sponge microRNA (miR)-217 to regulate the expression of PD-L1. In addition, Lnc-CCNH-8 can also stabilize PD-L1 through miR-3173/PKP3 axis. Furthermore, mice bearing tumors with high Lnc-CCNH-8 expression had significant therapeutic sensitivity to anti-PD-L1 monoclonal antibody treatment. More important, HCC patients with high levels of plasma exosomal Lnc-CCNH-8 had a better therapeutic response to ICIs. Taken together, our results reveal the function of Lnc-CCNH-8 in inducing immune escape from CD8+ T-cell-mediated killing by up-regulating PD-L1 in a miR-217/miR-3173-dependent manner, which also reveals a novel mechanism of PD-L1 regulation in HCC, and exosomal Lnc-CCNH-8 can serve as a predictive marker for immunotherapy response in HCC.
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