Böger Christine, Behrens Hans-Michael, Mathiak Micaela, Krüger Sandra, Kalthoff Holger, Röcken Christoph
Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
Department of Experimental Cancer Research, Christian-Albrechts-University, Kiel, Germany.
Oncotarget. 2016 Apr 26;7(17):24269-83. doi: 10.18632/oncotarget.8169.
Targeting the PD-1/PD-L1 immune checkpoint signaling is a novel promising treatment strategy in several tumor entities, and it is suggested that PD-L1/PD-1 expression is predictive for a PD-1/PD-L1 checkpoint inhibitor treatment response. We investigated the expression of PD-L1 and PD-1 by immunohistochemistry in a large and well characterized gastric cancer (GC) cohort of Caucasian patients, consisting of 465 GC samples and 15 corresponding liver metastases. Staining results were correlated with clinico-pathological characteristics and survival. PD-L1 expression was found in tumor cells of 140 GCs (30.1%) and 9 liver metastases (60%) respectively in immune cells of 411 GCs (88.4%) and 11 liver metastases (73.3%). PD-1 was expressed in tumor infiltrating lymphocytes in 250 GCs (53.8%) and in 11 liver metastases (73.3%). PD-L1 expression was significantly more prevalent in men, GCs of the proximal stomach, unclassified, papillary, Her2/neu-positive, Epstein-Barr-virus-positive, microsatellite instable, and PIK3CA-mutated GCs. A high PD-L1/PD-1 expression was associated with a significantly better patient outcome, and PD-L1 turned out to be an independent survival prognosticator. The correlation of PD-L1/PD-1 expression with distinct clinico-pathological patient characteristics may serve as a surrogate marker of PD-L1-positive GCs and may direct the use of immune checkpoint treatment strategies.
针对PD-1/PD-L1免疫检查点信号通路是多种肿瘤实体中一种新的有前景的治疗策略,并且提示PD-L1/PD-1表达可预测PD-1/PD-L1检查点抑制剂的治疗反应。我们通过免疫组织化学方法研究了一个由465例胃癌样本和15例相应肝转移灶组成的、特征明确的白种人胃癌(GC)队列中PD-L1和PD-1的表达情况。染色结果与临床病理特征及生存情况相关。在140例GC(30.1%)的肿瘤细胞和9例肝转移灶(60%)中发现了PD-L1表达,在411例GC(88.4%)和11例肝转移灶(73.3%)的免疫细胞中也发现了PD-L1表达。在250例GC(53.8%)的肿瘤浸润淋巴细胞和11例肝转移灶(73.3%)中表达了PD-1。PD-L1表达在男性、胃近端GC、未分类、乳头状、Her2/neu阳性、爱泼斯坦-巴尔病毒阳性、微卫星不稳定及PIK3CA突变的GC中明显更普遍。高PD-L1/PD-1表达与患者明显更好的预后相关,并且PD-L1被证明是一个独立的生存预后指标。PD-L1/PD-1表达与不同临床病理患者特征的相关性可作为PD-L1阳性GC的替代标志物,并可指导免疫检查点治疗策略的应用。