PD-L1 expression as a predictive biomarker for cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma
PD-L1 expression as a predictive biomarker for cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma
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PD-L1 表达作为肝细胞癌患者细胞因子诱导的杀伤细胞免疫治疗的预测生物标志物。
DOI：
10.1080/2162402x.2016.1176653
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发表时间：
2016-01-01
期刊：
影响因子：
7.2
通讯作者：
Xia, Jian-Chuan
中科院分区：
文献类型：
--
作者：
Chen, Chang-Long;Pan, Qiu-Zhong;Xia, Jian-Chuan
细胞因子诱导杀伤（CIK）细胞免疫疗法是治疗肝细胞癌（HCC）的有效治疗策略。然而，CIK细胞治疗的疗效可能会受到患者之间复杂免疫微环境差异的影响。在此，我们研究了肝癌患者CIK细胞免疫治疗中PD-L1表达与生存获益之间的关系。本回顾性研究纳入448例HCC患者：217例单独行肝切除术；231例患者接受肝切除术和术后CIK细胞输注。采用免疫组织化学方法检测所有患者肿瘤组织切片中PD-L1的表达。同时采用流式细胞术探讨HCC微环境中PD-L1表达与局部炎症反应的关系。我们发现CIK治疗组与单纯手术组相比，预后明显改善。在CIK治疗组中，在表现出长期生存益处的患者中观察到更高的PD-L1表达。生存分析显示，PD-L1表达>= 5%的患者比PD-L1表达1-5%或< 1%的患者有更好的总生存期（OS）和无复发生存期（RFS），特别是在高乙型肝炎病毒载量亚组中。相比之下，单独手术组PD-L1表达对患者的生存无直接影响。此外，PD-L1表达与HCC患者乙型肝炎病毒载量和肿瘤浸润淋巴细胞比例高度相关。总之，我们的研究表明，PD-L1表达可能反映了内源性宿主对肿瘤的免疫反应，并可作为预测HCC患者辅助CIK细胞免疫治疗的生存获益的生物标志物。
Cytokine-induced killer (CIK) cell immunotherapy represents an effective treatment strategy for treating hepatocellular carcinoma (HCC). However, the therapeutic benefits of CIK cell treatment can be influenced by differences in complex immune microenvironment between patients. Herein, we investigated the relationship between PD-L1 expression and survival benefits of CIK cell immunotherapy in HCC patients. This retrospective study included 448 HCC patients: 217 cases underwent hepatectomy alone; 231 cases received hepatectomy and post-operative CIK cell transfusion. Immunohistochemistry was used to measure PD-L1 expression in tumor tissue sections from all patients. Meanwhile, flow cytometry was performed to explore the relationship between PD-L1 expression and localized inflammatory response in HCC microenvironment. We found a significantly improved prognosis in CIK treatment group compared with surgery alone group. In the CIK treatment group, higher PD-L1 expression was observed in patients who exhibited long-term survival benefit. Survival analysis showed patients with >= 5% PD-L1 expression had better overall survival (OS) and recurrence-free survival (RFS) than patients with 1-5% or < 1% PD-L1 expression, particularly in the subgroup with high hepatitis B viral load. By contrast, PD-L1 expression did not show direct impact on the survival of patients in surgery alone group. Additionally, PD-L1 expression was found to be highly associated with hepatitis B viral load and the proportion of tumor-infiltrating lymphocytes in HCC patients. In conclusions, our study indicates that PD-L1 expression may reflect the presence of endogenous host immune response to tumor and serve as a biomarker for predicting survival benefits from adjuvant CIK cell immunotherapy in HCC patients.