Noh Byeong-Joo, Kim Ji Hoon, Eom Dae-Woon
Department of Pathology, University of Ulsan College of Medicine, Gangneung, Korea.
Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.
Ann Clin Lab Sci. 2018 Nov;48(6):695-706.
We categorized gastric cancers into four types of tumor immune microenvironment based on PD-L1 expression and tumor-infiltrating lymphocytes (TILs) to analyze clinicopathologic characteristics and recommend an immunotherapy-targetable subgroup.
Formalin-fixed, paraffin-embedded tissue samples of randomly selected gastric adenocarcinoma (n=479) were obtained and arrayed using a tissue-arraying instrument. Immunohistochemical stains for PD-L1, PD-1, and CD8 were performed and evaluated in addition to microsatellite instability, EBV infection, and HER-2 analyses.
Tumor microenvironment immune type (TMIT) I (both PD-L1-positive tumor cells & CD8-high TILs) and type III (PD-L1-positive tumor cells & CD8-low TILs) showed the best and worse prognosis, respectively. PD-L1 expression was significantly associated with Epstein-Barr virus infection (<0.001) and microsatellite instability status (<0.001). PD-L1 immunoreactivity was positively correlated with TILs having CD8 or PD-1 overexpression.
TMIT I subgroup showed more patent CD8/PD-L1/PD-1 signaling pathway compared to other types. Therefore, TMIT I subgroup is a good candidate to predict effective response rate for immune checkpoint blockers. Such stratification of gastric cancers into four types can be used to predict the prognosis of patients and determine the immunotherapy-targetable subgroup.
我们基于程序性死亡受体配体1（PD-L1）表达和肿瘤浸润淋巴细胞（TILs）将胃癌分为四种肿瘤免疫微环境类型，以分析临床病理特征并推荐一个可进行免疫治疗的亚组。
获取随机选择的胃腺癌（n = 479）的福尔马林固定、石蜡包埋组织样本，并使用组织阵列仪进行排列。除了进行微卫星不稳定性、EB病毒感染和人表皮生长因子受体2（HER-2）分析外，还进行了PD-L1、程序性死亡受体1（PD-1）和CD8的免疫组织化学染色及评估。
肿瘤微环境免疫类型（TMIT）I型（PD-L1阳性肿瘤细胞和CD8高表达TILs）和III型（PD-L1阳性肿瘤细胞和CD8低表达TILs）分别显示出最佳和最差的预后。PD-L1表达与EB病毒感染（<0.001）和微卫星不稳定性状态（<0.001）显著相关。PD-L1免疫反应性与CD8或PD-1过表达的TILs呈正相关。
与其他类型相比，TMIT I亚组显示出更明显的CD8/PD-L1/PD-1信号通路。因此，TMIT I亚组是预测免疫检查点阻断剂有效反应率的良好候选者。将胃癌分为四种类型的这种分层可用于预测患者的预后并确定可进行免疫治疗的亚组。
