Fontugne Jacqueline, Augustin Jérémy, Pujals Anaïs, Compagnon Philippe, Rousseau Benoit, Luciani Alain, Tournigand Christophe, Cherqui Daniel, Azoulay Daniel, Pawlotsky Jean-Michel, Calderaro Julien
AP-HP, Groupe Hospitalier Henri Mondor, Département de Pathologie, Créteil, France.
INSERM, U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.
Oncotarget. 2017 Apr 11;8(15):24644-24651. doi: 10.18632/oncotarget.15602.
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.
胆管癌是一种侵袭性胆管肿瘤，缺乏有效的治疗药物。在临床试验中，靶向PD-L1/PD-1免疫检查点的免疫疗法在实体癌和血液系统癌症中显示出令人鼓舞的结果。对这些免疫调节剂的反应与PD-L1表达相关。我们的目标是表征肝内胆管癌（iCCA）和肝门周围胆管癌（pCCA）中PD-L1的表达情况，并将我们的结果与临床病理特征、肿瘤浸润淋巴细胞（TIL）密度和PD-1表达相关联。
该研究纳入了一系列58例iCCA和41例pCCA。使用免疫组织化学研究PD-L1、PD-1和CD3的表达。通过对CD3染色的肿瘤内淋巴细胞进行定量评分，利用免疫组织化学评估TIL的密度。
在9例（9%，5例iCCA和4例pCCA）病例中观察到肿瘤细胞表达PD-L1。在46%（n = 46）的病例（31例iCCA和15例pCCA）中鉴定出PD-L1阳性炎症细胞聚集物。肿瘤细胞或炎症细胞表达PD-L1均与高密度的CD3阳性TIL相关（分别为p = 0.01和p = 0.005）。在PD-1高表达的肿瘤中，PD-L1阳性炎症细胞聚集物的数量更高（p < 0.0001）。
总体而言，iCCA和pCCA中的PD-L1主要在TIL密度高的肿瘤中表达。我们的结果表明，肿瘤内淋巴细胞浸润密集的CCA可能是PD-L1/PD-1阻断剂的良好候选者。
