Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Biomedical Knowledge Engineering Laboratory, Seoul National University School of Dentistry, Seoul, South Korea.
Histopathology. 2016 Jun;68(7):1079-89. doi: 10.1111/his.12882. Epub 2015 Dec 1.
To investigate the clinicopathological characteristics of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expression in the tumour microenvironments of diffuse large B cell lymphoma (DLBCL).
Tumour tissues from 126 DLBCL patients were immunostained for PD-L1 and PD-1. The expression of PD-L1 by tumour cells and/or tumour-infiltrating immune cells (mainly macrophages) was evaluated, and the number of tumour-infiltrating PD-1(+) cells was assessed. PD-L1 expression in tumour cells was observed in 61.1% of DLBCLs, with a weak intensity in 29.4%, moderate intensity in 21.4% and strong intensity in 10.3% of cases. Strong PD-L1 expression in tumour cells was associated significantly with the presence of B symptoms (adjusted P = 0.005) and Epstein-Barr virus (EBV) infection (adjusted P = 0.015), and tended to be higher in activated B cell-like immunophenotype (16.7%) than germinal centre B cell-like immunophenotype (2.5%) (adjusted P = 0.271). DLBCLs with PD-L1 expression in tumour cells/macrophages showed similar clinicopathological characteristics. The quantity of PD-1(+) tumour-infiltrating lymphocytes correlated positively with the level of PD-L1 expression in tumour cells (P = 0.042) or in tumour cells/macrophages (P = 0.03). Increased infiltration of PD-1(+) cells was associated with prolonged progression-free survival (P = 0.005) and overall survival (P = 0.026) in DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), whereas PD-L1 expression had no prognostic significance.
PD-L1 and PD-1 were expressed variably in DLBCLs by tumour cells and tumour-infiltrating immune cells and might be potential therapeutic targets using PD-1/PD-L1 blockade.
研究程序性死亡配体 1（PD-L1）和程序性死亡受体 1（PD-1）在弥漫性大 B 细胞淋巴瘤（DLBCL）肿瘤微环境中的表达的临床病理特征。
对 126 例 DLBCL 患者的肿瘤组织进行 PD-L1 和 PD-1 的免疫染色。评估肿瘤细胞和/或肿瘤浸润免疫细胞（主要为巨噬细胞）中 PD-L1 的表达，并评估肿瘤浸润 PD-1（+）细胞的数量。在 61.1%的 DLBCL 中观察到肿瘤细胞 PD-L1 表达，其中弱强度占 29.4%，中等强度占 21.4%，强强度占 10.3%。肿瘤细胞中强烈的 PD-L1 表达与 B 症状的存在显著相关（调整 P = 0.005）和 EBV 感染（调整 P = 0.015），在活化 B 细胞样免疫表型中倾向于更高（16.7%）而不是生发中心 B 细胞样免疫表型（2.5%）（调整 P = 0.271）。PD-L1 在肿瘤细胞/巨噬细胞中表达的 DLBCL 具有相似的临床病理特征。PD-1（+）肿瘤浸润淋巴细胞的数量与肿瘤细胞 PD-L1 表达水平呈正相关（P = 0.042）或与肿瘤细胞/巨噬细胞 PD-L1 表达水平呈正相关（P = 0.03）。在接受利妥昔单抗-环磷酰胺、多柔比星、长春新碱、泼尼松（R-CHOP）治疗的 DLBCL 患者中，PD-1（+）细胞浸润增加与无进展生存（P = 0.005）和总生存（P = 0.026）延长相关，而 PD-L1 表达无预后意义。
PD-L1 和 PD-1 在 DLBCL 中由肿瘤细胞和肿瘤浸润免疫细胞表达不同，可能成为使用 PD-1/PD-L1 阻断的潜在治疗靶点。
