PD-L1 在结直肠癌中是一把双刃剑：PD-L1 的预后价值取决于表达 PD-L1 的细胞类型。
PD-L1 is a double-edged sword in colorectal cancer: the prognostic value of PD-L1 depends on the cell type expressing PD-L1.
机构信息
Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
出版信息
J Cancer Res Clin Oncol. 2019 Jul;145(7):1785-1794. doi: 10.1007/s00432-019-02942-y. Epub 2019 May 25.
PURPOSE
To investigate the associations between programmed cell death ligand-1 (PD-L1) on tumor cells (TCs) or PD-L1 on tumor-infiltrating immune cells (TIICs) and the microsatellite instability (MSI) status in colorectal cancer (CRC).
METHODS
In total, 238 CRC patients were enrolled. PD-L1 expression and MSI status were studied by immunohistochemical staining and polymerase chain reaction. The χ test was used to compare characteristics. The Kaplan-Meier method was used for survival analysis. Cox proportional hazards models were used to determine the prognostic influence of clinicopathological factors.
RESULTS
Eighteen patients (7.6%) were had MSI-high (MSI-H) CRC. The number of patients with PD-L1 expression on TCs, stromal TIICs and intraepithelial TIICs was 13 (5.5%), 64 (26.9%) and 45 (18.9%), respectively. The MSI-H phenotype was significantly associated with younger age, right sidedness, mucinous component, high grade, stromal TIICs expressing PD-L1 (P = 0.042) and intraepithelial TIICs expressing PD-L1 (P < 0.001), but not TCs expressing PD-L1. PD-L1-expressing TCs were an independent marker of poor prognosis [hazard ratio (HR) = 3.387, P = 0.003], and PD-L1-expressing stromal TIICs were an independent marker of good prognosis (HR = 0.551, P < 0.001).
CONCLUSIONS
PD-L1-expressing TCs were a marker of poor prognosis; in contrast, PD-L1-expressing TIICs were a marker of good prognosis. The MSI-H phenotype was associated with the presence of PD-L1-expressing TIICs, but not of PD-L1-expressing TCs.
目的
研究肿瘤细胞（TCs）上的程序性细胞死亡配体-1（PD-L1）或肿瘤浸润免疫细胞（TIICs）上的 PD-L1 与结直肠癌（CRC）微卫星不稳定性（MSI）状态之间的关联。
方法
共纳入 238 例 CRC 患者。通过免疫组织化学染色和聚合酶链反应研究 PD-L1 表达和 MSI 状态。使用 χ 检验比较特征。采用 Kaplan-Meier 法进行生存分析。使用 Cox 比例风险模型确定临床病理因素的预后影响。
结果
18 例（7.6%）患者为 MSI-高（MSI-H）CRC。TCs、基质 TIICs 和上皮内 TIICs 表达 PD-L1 的患者分别为 13 例（5.5%）、64 例（26.9%）和 45 例（18.9%）。MSI-H 表型与年龄较轻、右侧、黏液成分、高级别、表达 PD-L1 的基质 TIICs（P=0.042）和上皮内 TIICs（P<0.001）显著相关，但与表达 PD-L1 的 TCs 无关。表达 PD-L1 的 TCs 是预后不良的独立标志物[风险比（HR）=3.387，P=0.003]，而表达 PD-L1 的基质 TIICs 是预后良好的独立标志物（HR=0.551，P<0.001）。
结论
表达 PD-L1 的 TCs 是预后不良的标志物；相反，表达 PD-L1 的 TIICs 是预后良好的标志物。MSI-H 表型与表达 PD-L1 的 TIICs 相关，而与表达 PD-L1 的 TCs 无关。
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