胸腺瘤和胸腺癌中 PD-L1 和 PD-1 的表达模式、预后价值和肿瘤内异质性。
Expression Patterns, Prognostic Value, and Intratumoral Heterogeneity of PD-L1 and PD-1 in Thymoma and Thymic Carcinoma.
机构信息
Division of Medical Oncology, Department of Internal Medicine, Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio.
Helen and Gary Gray Cancer Center, Hartford Hospital, and University of Connecticut School of Medicine, Hartford, Connecticut.
出版信息
J Thorac Oncol. 2018 Aug;13(8):1204-1212. doi: 10.1016/j.jtho.2018.04.013. Epub 2018 Apr 24.
INTRODUCTION
Thymic epithelial tumors (TETs) including thymoma and thymic carcinoma are rare tumors with little data available to guide treatment. Immunotherapy with checkpoint blockade has shown promising activity, but data regarding the expression patterns and prognostic implications of programmed death 1 (PD-1) and its ligand (PD-L1) in TETs have yielded conflicting results. Intratumoral heterogeneity of PD-1/L1 expression has been shown in other cancers, but has not been described in the TET literature.
METHODS
We performed a retrospective single-center review of 35 patients with resected TET. PD-1/L1 expression was assessed by immunohistochemistry using PD-1 clone: NAT105 and PD-L1 clone: 22C3. Tumor samples from 35 patients were evaluated including 32 patients with thymoma and 3 patients with thymic carcinoma.
RESULTS
PD-L1 expression was detected in 83% (29 of 35) tumor samples, including 100% (3 of 3) of thymic carcinoma patients and 81% (26 of 32) of thymoma patients. PD-1 expression was detected in 77% (27 of 35), including 33% (1 of 3) of thymic carcinoma patients and 81% (26 of 32) thymoma patients. High PD-1 expression was associated with lower grade tumors. Unlike prior studies, PD-L1 expression was not associated with higher grade tumors or higher stage. Neither PD-L1 nor PD-1 expression was significantly associated with survival. Three patients with thymoma had multiple tumor sections evaluated for expression of PD-1/L1, with differing expression patterns of both PD-L1 and PD-1 observed in two patients.
CONCLUSIONS
This study confirms high expression of PD-L1 and PD-1 in TET and shows for the first time intratumoral heterogeneity of PD-L1 and PD-1 in thymoma patients.
简介
胸腺瘤和胸腺癌等胸内上皮性肿瘤是罕见肿瘤，治疗相关数据较少。免疫检查点抑制剂治疗显示出有前景的活性，但程序性死亡受体 1（PD-1）及其配体（PD-L1）在胸内上皮性肿瘤中的表达模式和预后意义的数据结果相互矛盾。其他癌症中已显示出 PD-1/L1 表达的肿瘤内异质性，但在胸内上皮性肿瘤文献中尚未描述。
方法
我们对 35 例接受手术治疗的胸内上皮性肿瘤患者进行了回顾性单中心研究。使用 PD-1 克隆：NAT105 和 PD-L1 克隆：22C3 通过免疫组织化学法评估 PD-1/L1 的表达。评估了 35 例患者的肿瘤样本，包括 3 例胸腺癌患者和 32 例胸腺瘤患者。
结果
在 83%（35 例中的 29 例）肿瘤样本中检测到 PD-L1 表达，包括 100%（3 例中的 3 例）胸腺癌患者和 81%（32 例中的 26 例）胸腺瘤患者。在 77%（35 例中的 27 例）肿瘤样本中检测到 PD-1 表达，包括 33%（3 例中的 1 例）胸腺癌患者和 81%（32 例中的 26 例）胸腺瘤患者。高 PD-1 表达与肿瘤分级较低相关。与先前的研究不同，PD-L1 表达与肿瘤分级较高或分期较高无关。PD-L1 和 PD-1 的表达均与生存无显著相关性。3 例胸腺瘤患者有多个肿瘤切片进行 PD-1/L1 表达评估，其中 2 例患者观察到 PD-L1 和 PD-1 的表达模式不同。
结论
本研究证实了胸内上皮性肿瘤中 PD-L1 和 PD-1 的高表达，并首次显示了胸腺瘤患者中 PD-L1 和 PD-1 的肿瘤内异质性。
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