程序性死亡配体1在肝细胞癌中的表达：与临床和病理特征的

StephenW

Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship With clinical and pathological featuresAuthors

• First published: 9 August 2016Full publication history
• DOI: 10.1002/hep.28710View/save citation
• Cited by: 0 articles
  

• 
• Funding Information
  

• Potential conflict of interest: Nothing to report.
• Supported by a grant from the Viruses, Immunity, and Cancers Department.
• See Editorial on Page 1847
  

AbstractThe prognosis of hepatocellular carcinoma (HCC) remains poor, with only one third of patients eligible for curative treatments and very limited survival benefits with the use of sorafenib, the current standard of care for advanced disease. Recently, agents targeting the programmed death ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) immune checkpoint were shown to display impressive antitumor activity in various solid or hematological malignancies, including HCC. PD-L1 immunohistochemical expression is thought to represent a biomarker predictive of drug sensitivity. Here, we investigated PD-L1 expression in a series of 217 HCCs and correlated our results with clinical and histological features and immunohistochemical markers (PD-1, cytokeratin 19, glutamine synthetase, and β-catenin expression). PD-L1 expression by neoplastic cells was significantly associated with common markers of tumor aggressiveness (high serum alpha-fetoprotein levels, P = 0.038; satellite nodules, P < 0.001; macrovascular invasion, P < 0.001; microvascular invasion, P < 0.001; poor differentiation, P < 0.001) and with the progenitor subtype of HCC (cytokeratin 19 expression, P = 0.031). High PD-L1 expression by inflammatory cells from the tumor microenvironment also correlated with high serum alpha-fetoprotein levels (P < 0.001), macrovascular invasion (P = 0.001), poor differentiation (P = 0.001), high PD-1 expression (P < 0.001), and the so-called lymphoepithelioma-like histological subtype of HCC (P = 0.003). Conclusion: PD-L1 expression by either neoplastic or intratumoral inflammatory cells is related to tumor aggressiveness and suggests that the response to treatments targeting the PD-L1/PD-1 immune checkpoint could be restricted to particular HCC variants; thus, enrichment of these tumor subtypes in future clinical trials should be considered. (Hepatology 2016;64:2038-2046)

StephenW

程序性死亡配体1在肝细胞癌中的表达：与临床和病理特征的关系
作者

    首次发布：9八月2016完整的出版历史
    DOI：10.1002 / hep.28710查看/保存引文
    引用：0文章

    文章的得分为1
    资金信息

    潜在利益冲突：没有报告。

    由病毒，免疫和癌症部门的资助支持。

    见第1847页的编辑

抽象

肝细胞癌（HCC）的预后仍然很差，仅有三分之一的患者符合治疗性治疗，并且使用索拉非尼是目前的晚期疾病护理标准，其生存获益非常有限。最近，靶向程序性死亡配体1（PD-L1）/程序性死亡受体1（PD-1）免疫检查点的药剂显示在各种固体或血液恶性肿瘤（包括HCC）中显示出令人印象深刻的抗肿瘤活性。 PD-L1免疫组织化学表达被认为代表预示药物敏感性的生物标志物。在这里，我们调查了一系列217 HCC的PD-L1表达，并将我们的结果与临床和组织特征和免疫组化标记（PD-1，细胞角蛋白19，谷氨酰胺合成酶和β-连环蛋白表达）相关联。肿瘤细胞的PD-L1表达与肿瘤侵袭性（高血清甲胎蛋白水平，P = 0.038;卫星结节，P <0.001;大血管入侵，P <0.001;微血管浸润，P <0.001）分化，P <0.001）和HCC的祖细胞亚型（细胞角蛋白19表达，P = 0.031）。来自肿瘤微环境的炎症细胞的高PD-L1表达也与高血清甲胎蛋白水平（P <0.001），大血管入侵（P = 0.001），差分化差（P = 0.001），高PD-1表达<0.001）和所谓的淋巴上皮瘤样组织学亚型的HCC（P = 0.003）。结论：通过肿瘤或肿瘤内炎症细胞的PD-L1表达与肿瘤侵袭性相关，并且表明针对PD-L1 / PD-1免疫检查点的治疗的应答​​可以限于特定的HCC变体;因此，应考虑这些肿瘤亚型在未来的临床试验中的富集。 （Hepatology 2016; 64：2038-2046）