Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.
Department of Pathology, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-Si, Kangwon-Do, 200-722, Republic of Korea.
J Neurooncol. 2018 Feb;136(3):453-461. doi: 10.1007/s11060-017-2675-6. Epub 2017 Nov 16.
The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation assay and fluorescence in situ hybridization (FISH) for the assessment of 1p/19q deletion were performed. Expression of PD-L1 in tumour cells and TIIs was found in 37 (32.2%) and 6 (5.2%) patients, respectively. Kaplan-Meier analysis indicated that PD-L1 expression in tumour cells was significantly associated with poor overall survival (OS) (P = 0.017), though multivariate Cox analysis did not confirm this association (hazard ratio 1.204; P = 0.615). PD-L1 expression in TIIs did not correlate with the patient prognosis (P = 0.545). In addition, MGMT methylation and IDH-1 (R132H) expression were associated with a better prognosis (P < 0.001 and P = 0.024, respectively). The expression of PD-L1 was associated with CD3-positive T-cell infiltration (P < 0.001), and IDH-1 wild type status (P = 0.008). A deeper insight into PD-L1 expression could help to ensure the success of future immunotherapy in GBM. Our study suggested that PD-L1 target therapy might be beneficial for PD-L1-expressing GBM patients with a poor prognosis.
本研究旨在确定程序性死亡配体 1(PD-L1)在胶质母细胞瘤(GBM)中的表达的临床病理意义。在 115 例连续 GBM 患者的回顾性队列中,使用免疫组织化学(IHC)测定 PD-L1 表达。膜性和纤维状 PD-L1 在>5%肿瘤细胞和肿瘤浸润免疫细胞(TII)中的任何强度染色被认为是阳性染色。此外,使用免疫组化检测异柠檬酸脱氢酶 1(IDH-1)(R132H)表达和分化簇 3(CD3)阳性 T 细胞浸润。进行 O(6)-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子甲基化测定和荧光原位杂交(FISH)以评估 1p/19q 缺失。在肿瘤细胞和 TII 中分别发现 PD-L1 表达在 37(32.2%)和 6(5.2%)患者中。Kaplan-Meier 分析表明,肿瘤细胞中 PD-L1 的表达与总体生存(OS)不良显著相关(P=0.017),尽管多变量 Cox 分析并未证实这种相关性(风险比 1.204;P=0.615)。TII 中 PD-L1 的表达与患者预后无关(P=0.545)。此外,MGMT 甲基化和 IDH-1(R132H)表达与更好的预后相关(P<0.001 和 P=0.024)。PD-L1 的表达与 CD3 阳性 T 细胞浸润相关(P<0.001),并且与 IDH-1 野生型状态相关(P=0.008)。对 PD-L1 表达的更深入了解有助于确保未来 GBM 免疫治疗的成功。我们的研究表明,PD-L1 靶向治疗可能对预后不良的 PD-L1 表达型 GBM 患者有益。