Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients.
Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients.
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DOI：
10.18632/oncotarget.15465
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发表时间：
2017-04-18
期刊：
影响因子：
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通讯作者：
Lee HS
中科院分区：
文献类型：
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作者：
Koh J;Ock CY;Kim JW;Nam SK;Kwak Y;Yun S;Ahn SH;Park DJ;Kim HH;Kim WH;Lee HS
我们共同评估了胃癌 (GC) 中的 PD-L1 表达和 CD8+ 肿瘤浸润淋巴细胞，并将其分为 4 种微环境免疫类型。对 392 例接受根治性手术和基于氟嘧啶的辅助化疗治疗的 II/III 期 GC 进行免疫组织化学（PD-L1、CD8、Foxp3、E-cadherin 和 p53）、PD-L1 mRNA 原位杂交 (ISH)、微卫星不稳定性 (MSI) 和 EBV ISH，并分析两个公共基因组数据库进行验证。在 98/392 个 GC 中发现了 PD-L1+ (25.0%)。免疫类型比例如下：PD-L1+/CD8High，22.7%； PD-L1−/CD8低，22.7%； PD-L1+/CD8低，2.3%； PD-L1−/CD8高，52.3%。 PD-L1+/CD8High 型占 EBV+ 和 MSI 高 (MSI-H) GC 的大部分（分别为 92.0% 和 66.7%），公共数据集的基因组分析显示了类似的模式。 PD-L1−/CD8High 显示出最佳的总生存期 (OS)，PD-L1−/CD8Low 表现最差（P < 0.001）。 PD-L1 表达单独与 OS 无关，然而，通过多变量分析，与 PD-L1+/CD8High 类型相比，PD-L1−/CD8High 类型是 OS 的独立有利预后因素 (P = 0.042)。最近基于 EBV、MSI、E-钙粘蛋白和 p53 的分子分类的调整显示没有显着的生存差异。这些发现支持基于 PD-L1/CD8 状态的免疫类型与 EBV+、MSI-H GC 之间的密切关系及其在 II/III 期 GC 中的预后意义。
We co-assessed PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in gastric cancer (GC), and categorized into 4 microenvironment immune types. Immunohistochemistry (PD-L1, CD8, Foxp3, E-cadherin, and p53), PD-L1 mRNA in situ hybridization (ISH), microsatellite instability (MSI), and EBV ISH were performed in 392 stage II/III GCs treated with curative surgery and fluoropyrimidine-based adjuvant chemotherapy, and two public genome databases were analyzed for validation. PD-L1+ was found in 98/392 GCs (25.0%). The proportions of immune types are as follows: PD-L1+/CD8High, 22.7%; PD-L1−/CD8Low, 22.7%; PD-L1+/CD8Low, 2.3%; PD-L1−/CD8High, 52.3%. PD-L1+/CD8High type accounted for majority of EBV+ and MSI-high (MSI-H) GCs (92.0% and 66.7%, respectively), and genome analysis from public datasets demonstrated similar pattern. PD-L1−/CD8High showed the best overall survival (OS) and PD-L1−/CD8Low the worst (P < 0.001). PD-L1 expression alone was not associated with OS, however, PD-L1−/CD8High type compared to PD-L1+/CD8High was independent favorable prognostic factor of OS by multivariate analysis (P = 0.042). Adaptation of recent molecular classification based on EBV, MSI, E-cadherin, and p53 showed no significant survival differences. These findings support the close relationship between PD-L1/CD8 status based immune types and EBV+, MSI-H GCs, and their prognostic significance in stage II/III GCs.