Center of Therapeutic Research for Hepatocellular Carcinoma, Beijing 302 Hospital, Beijing, China.
PLoS One. 2011;6(9):e23621. doi: 10.1371/journal.pone.0023621. Epub 2011 Sep 1.
The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC).
METHODOLOGY/PRINCIPAL FINDINGS: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation.
CONCLUSIONS/SIGNIFICANCE: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma.
程序性细胞死亡受体 1/配体 1（PD-1/PD-L1）通路在肿瘤逃避宿主免疫方面起着至关重要的作用。本研究旨在评估乙型肝炎病毒（HBV）相关肝细胞癌（HCC）患者冷冻消融后循环 PD-L1/PD-1 与预后的关系。
方法/主要发现：本研究纳入了 141 例 HBV 相关 HCC 患者，其中 109 例患者接受了冷冻消融治疗。通过流式细胞术检测循环 PD-L1/PD-1 的表达，同时对 23 例患者进行肿瘤内 PD-L1 表达的免疫组化染色评估。循环 PD-1/PD-L1 的表达与 HCC 患者疾病的严重程度相关，并且循环 PD-L1 的表达与肿瘤内 PD-L1 的表达密切相关。在临床参数中，PD-1/PD-L1 的表达与肿瘤大小、血管侵犯和 BCLC 分期有关。此外，冷冻消融后 PD-1/PD-L1 的表达下降，而在肿瘤复发时升高。循环 PD-L1 和 PD-1 表达较高的患者总生存和无瘤生存明显短于表达较低的患者。多因素分析证实，循环 PD-L1 可作为 HCC 患者冷冻消融后总生存和肿瘤复发生存的独立预测因子。
结论/意义：循环 PD-L1/PD-1 的上调与 HBV 相关肝细胞癌患者冷冻消融后预后不良有关。
