Clinical impact of programmed cell death ligand 1 expression in colorectal cancer
Clinical impact of programmed cell death ligand 1 expression in colorectal cancer
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DOI：
10.1016/j.ejca.2013.02.015
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发表时间：
2013-06-01
影响因子：
8.4
通讯作者：
Tornillo, Luigi
中科院分区：
文献类型：
--
作者：
Droeser, Raoul A.;Hirt, Christian;Tornillo, Luigi
背景：由PD配体1（PD-L1）触发的程序性细胞死亡1（PD-1）受体抑制T细胞活化。PD-L1表达在不同的恶性肿瘤中被检测到，并且与不良预后相关。材料和方法：用两种PD-L1特异性抗体制剂对包括健康结肠粘膜和临床注释的结直肠癌（CRC）标本的组织微阵列（n = 1491）进行染色。手术切除的CRC标本进行酶消化和分析分化簇8（CD 8）和PD-1 expression.Results：强PD-L1的表达观察到37%的错配修复（MMR）-熟练和29%的MMR-缺陷的CRC。在MMR阳性的CRC中，PD-L1强表达与不表达PD-1的CD 8（+）淋巴细胞浸润相关（P = 0.0001）。在单变量分析中，在训练集（P = 0.0001）和验证集（P = 0.03）中，MMR-proficient CRC中的强PD-L1表达与早期T分期、无淋巴结转移、肿瘤分级较低、无血管浸润和生存率显著提高显著相关。在多因素分析中也检测到类似的趋势（P = 0.052），包括年龄、性别、T分期、N分期、肿瘤分级、血管浸润、浸润边缘和MMR状态。有趣的是，程序性死亡受体配体1（PDL-1）和干扰素（IFN）-γ基因表达，通过定量逆转录聚合酶链反应（RT-PCR）检测新鲜冷冻的CRC标本（n = 42）被发现显着相关（r = 0.33，P = 0.03）。(C)2013爱思唯尔有限公司保留所有权利。
Background: Programmed cell death 1 (PD-1) receptor triggering by PD ligand 1 (PD-L1) inhibits T cell activation. PD-L1 expression was detected in different malignancies and associated with poor prognosis. Therapeutic antibodies inhibiting PD-1/PD-L1 interaction have been developed.Materials and methods: A tissue microarray (n = 1491) including healthy colon mucosa and clinically annotated colorectal cancer (CRC) specimens was stained with two PD-L1 specific antibody preparations. Surgically excised CRC specimens were enzymatically digested and analysed for cluster of differentiation 8 (CD8) and PD-1 expression.Results: Strong PD-L1 expression was observed in 37% of mismatch repair (MMR)-proficient and in 29% of MMR-deficient CRC. In MMR-proficient CRC strong PD-L1 expression correlated with infiltration by CD8(+) lymphocytes (P = 0.0001) which did not express PD-1. In univariate analysis, strong PD-L1 expression in MMR-proficient CRC was significantly associated with early T stage, absence of lymph node metastases, lower tumour grade, absence of vascular invasion and significantly improved survival in training (P = 0.0001) and validation (P = 0.03) sets. A similar trend (P = 0.052) was also detectable in multivariate analysis including age, sex, T stage, N stage, tumour grade, vascular invasion, invasive margin and MMR status. Interestingly, programmed death receptor ligand 1 (PDL-1) and interferon (IFN)-gamma gene expression, as detected by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in fresh frozen CRC specimens (n = 42) were found to be significantly associated (r = 0.33, P = 0.03).Conclusion: PD-L1 expression is paradoxically associated with improved survival in MMR-proficient CRC. (C) 2013 Elsevier Ltd. All rights reserved.