Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer
Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer
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DOI：
10.1158/1078-0432.ccr-04-1469
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发表时间：
2005-04-15
影响因子：
11.5
通讯作者：
Nakajima, Y
中科院分区：
文献类型：
--
作者：
Ohigashi, Y;Sho, M;Nakajima, Y
目的：程序性死亡-1/程序性死亡-1配体（PD-1/PD-L）负调控T细胞活化途径在肿瘤逃避宿主免疫中起重要作用。本研究旨在探讨PD-L1和PD-L2在食管癌组织中的表达及其对食管癌术后患者预后的影响。实验设计：采用实时荧光定量PCR方法检测41例食管癌切除术后患者PD-L1和PD-L2基因的表达。结果：免疫组化和实时荧光定量PCR检测PD-L1和PD-L2的mRNA水平与蛋白表达密切相关。PD-L阳性患者的预后明显差于阴性患者。这在肿瘤的晚期比早期更明显。多因素分析显示PD-L状态是独立的预后因素。结论：PD-L1和PD-L2的表达可能是食管癌患者预后的一个新的预测指标，并为靶向PD-1/PD-L通路的新型免疫治疗提供了理论依据。
Purpose: The negative regulatory programmed death-1/programmed death-1 ligand (PD-1/PD-L) pathway in T-cell activation has been suggested to play an important role in tumor evasion from host immunity. In this study, we investigated the expression of PD-L1 and PD-L2 in human esophageal cancer to define their clinical significance in patients' prognosis after surgery.Experimental Design: PD-L1 and PD-L2 gene expression was evaluated in 41 esophagectomy patients by real-time quantitative PCR. The protein expression was also evaluated with newly generated monoclonal antibodies that recognize human PD-L1 (MIH1) and PD-L2 (MIH18).Results: The protein and the m RNA levels of determination by immunohistochemistry and realtime quantitative PCR were closely correlated. PD-L-positive patients had a significantly poorer prognosis than the negative patients. This was more pronounced in the advanced stage of tumor than in the early stage. Furthermore, multivariate analysis indicated that PD-L status was an independent prognostic factor. Although there was no significant correlation between PD-L1 expression and tumor-infiltrating T lymphocytes, PD-L2 expression was inversely correlated with tumor-infiltrating CD8(+) Tcells.Conclusions: These data suggest that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targeting PD-1/PD-L pathway.