Cho Junhun, Lee Jeeyun, Bang Heejin, Kim Seung Tae, Park Se Hoon, An Ji Yeong, Choi Min Gew, Lee Joon Ho, Sohn Tae Sung, Bae Jae Moon, Kang Won Ki, Kim Sung, Kim Kyoung-Mee
Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oncotarget. 2017 Feb 21;8(8):13320-13328. doi: 10.18632/oncotarget.14519.
Programmed death-ligand 1 (PD-L1) is expressed in a subgroup of gastric cancers that may benefit from immunotherapy. Microsatellite instability-high (MSI-H) is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1. The relationship between PD-L1 expression and MSI-H status remains poorly understood. In this study, we investigated PD-L1 expression in patients with MSI-H gastric cancer. We analyzed PD-L1 expression in 78 MSI-H gastric cancer tissue samples using immunohistochemistry. PD-L1 expression was classified as expression on tumor cells or on immune cells. We observed PD-L1 expression in 48 gastric cancer samples (61.5%), consisting of 7 (9.0%) cases with tumor PD-L1 expression and 47 (60.3%) cases with immune cell PD-L1 expression. Immune cell PD-L1 expression was frequently associated with intestinal type cancer by the Lauren classification (p = 0.015), with a lower risk of lymph node metastasis (p = 0.027) and lower tumor stages (p = 0.029) compared to MSI-H gastric cancers without PD-L1 expression. Moreover, immune cell PD-L1 expression was an independent favorable prognostic factor for overall survival (versus PD-L1 negative; hazard ratio, 3.451; 95% confidence interval, 1.172-12.745; p = 0.025). In MSI-H gastric cancer, PD-L1 expression was observed to be independently associated with a longer survival.
程序性死亡配体1（PD-L1）在一部分可能从免疫治疗中获益的胃癌中表达。微卫星高度不稳定（MSI-H）是针对PD-1或其配体PD-L1的免疫治疗反应的潜在预测因素。PD-L1表达与MSI-H状态之间的关系仍知之甚少。在本研究中，我们调查了MSI-H胃癌患者的PD-L1表达情况。我们使用免疫组织化学分析了78例MSI-H胃癌组织样本中的PD-L1表达。PD-L1表达分为肿瘤细胞或免疫细胞上的表达。我们在48例胃癌样本（61.5%）中观察到PD-L1表达，其中7例（9.0%）为肿瘤PD-L1表达，47例（60.3%）为免疫细胞PD-L1表达。根据劳伦分类，免疫细胞PD-L1表达常与肠型癌相关（p = 0.015），与无PD-L1表达的MSI-H胃癌相比，淋巴结转移风险较低（p = 0.027），肿瘤分期较低（p = 0.029）。此外，免疫细胞PD-L1表达是总生存的独立有利预后因素（与PD-L1阴性相比；风险比，3.451；95%置信区间，1.172 - 12.745；p = 0.025）。在MSI-H胃癌中，观察到PD-L1表达与更长的生存期独立相关。
