Programmed Death Ligand 1 Expression in Hepatocellular Carcinoma: Relationship With Clinical and Pathological Features
Programmed Death Ligand 1 Expression in Hepatocellular Carcinoma: Relationship With Clinical and Pathological Features
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DOI：
10.1002/hep.28710
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发表时间：
2016-12-01
期刊：
影响因子：
13.5
通讯作者：
Pawlotsky, Jean-Michel
中科院分区：
文献类型：
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作者：
Calderaro, Julien;Rousseau, Benoit;Pawlotsky, Jean-Michel
肝细胞癌的预后仍然很差，只有三分之一的患者有资格接受根治治疗，使用索拉非尼的生存益处非常有限，索拉非尼是目前治疗晚期疾病的标准药物。最近，针对程序性死亡配体1(PD-L1)/程序性死亡受体1(PD-1)免疫检查点的药物在包括肝癌在内的各种实体或血液系统恶性肿瘤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是预测药物敏感性的生物标志物。在这里，我们研究了一系列217例肝癌中PD-L1的表达，并将我们的结果与临床和组织学特征以及免疫组织化学标记物(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PD-L1的表达与肿瘤侵袭性的共同标记物显著相关(高血清甲胎蛋白水平，P=0.038；卫星结节，P<；0.001；大血管侵犯，P<；0.001；微血管侵犯，P<；0.001；分化差，P<；0.001)以及肝细胞癌的前体亚型(细胞角蛋白19表达，P=0.031)。肿瘤微环境中炎性细胞的高PD-L1表达还与血清甲胎蛋白水平高(P<；0.001)、大血管侵犯(P=0.001)、低分化(P=0.001)、PD-1高表达(P<；0.001)以及所谓的淋巴上皮瘤样组织亚型(P=0.003)相关。结论：肿瘤或瘤内炎性细胞的PD-L1表达与肿瘤侵袭性有关，提示针对PD-L1/PD-1免疫检查点的治疗反应可能仅限于特定的肝癌变异；因此，在未来的临床试验中应考虑丰富这些肿瘤亚型。
The 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 beta-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 lymphoepithe-lioma-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.