PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma.
PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma.
复制标题
DOI：
10.18632/oncotarget.15602
复制
发表时间：
2017-04-11
期刊：
影响因子：
--
通讯作者：
Calderaro J
中科院分区：
文献类型：
--
作者：
Fontugne J;Augustin J;Pujals A;Compagnon P;Rousseau B;Luciani A;Tournigand C;Cherqui D;Azoulay D;Pawlotsky JM;Calderaro J
胆管细胞癌是一种侵袭性胆道肿瘤，缺乏有效的治疗药物。针对PD-L1/PD-1免疫检查点的免疫疗法在临床试验中对实体癌和血液病显示了令人鼓舞的结果。对这些免疫调节剂的反应与PD-L1的表达有关。我们的目标是研究PD-L1在肝内胆管细胞癌(ICCA)和肝门周围胆管细胞癌(PCCA)中的表达特征，并探讨其与临床病理特征、肿瘤浸润性淋巴细胞(TIL)密度和PD-1表达的相关性。这项研究包括一系列58个iCCA和41个pCCA。免疫组织化学方法检测PD-L1、PD-1和CD3的表达。用CD3染色的瘤内淋巴细胞定量记分，用免疫组织化学方法评价TIL的密度。肿瘤细胞表达PD-L1者9例(9%)，其中5例为iCca，4例为pCca。46%(n=46)的病例(31例iCCA和15例pCCA)可见PD-L1阳性炎症细胞聚集体。肿瘤细胞或炎性细胞的PD-L1表达与CD3阳性TIL的高密度相关(分别为p=0.01和p=0.005)。在PD-1高表达的肿瘤中，PD-L1阳性炎症细胞聚集体的数量较多(p<；0.0001)。总之，PD-L1在iCCA和pCCA中主要在TIL密度高的肿瘤中表达。我们的结果提示，瘤内淋巴细胞密集的CCA可能是PD-L1/PD-1阻滞剂的良好候选者。
Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression. A series of 58 iCCAs and 41 pCCAs was included in the study. PD-L1, PD-1 and CD3 expression was investigated using immunohistochemistry. Density of TILs was evaluated by immunohistochemistry using a quantitative score of CD3-stained intratumoral lymphocytes. PD-L1 expression by neoplastic cells was observed in 9 cases (9%, 5 iCCAs and 4 pCCAs). PD-L1 positive inflammatory cell aggregates were identified in 46% (n = 46) of the cases (31 iCCAs and 15 pCCAs). PD-L1 expression by either neoplastic or inflammatory cells was associated to high density of CD3-positive TILs (p = 0.01 and p = 0.005, respectively). The number of PD-L1 positive inflammatory cell aggregates was higher in tumors with high PD-1 expression (p < 0.0001). Altogether, PD-L1 in iCCA and pCCA is mainly expressed in tumors with high density of TILs. Our results suggest that CCAs with dense intratumoral lymphocytic infiltration might represent good candidates for PD-L1/PD-1 blocking agents.