Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma
Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma
复制标题
PD-L1 的过度表达与人类肝细胞癌的肿瘤侵袭性和术后复发显着相关。
DOI：
10.1158/1078-0432.ccr-08-1608
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发表时间：
2009-02-01
影响因子：
11.5
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Gao, Qiang;Wang, Xiao-Ying;Fan, Jia
目的：肿瘤细胞上程序性细胞死亡1配体1和2（PD - Ls）的异常表达抑制抗肿瘤免疫，导致肿瘤免疫逃逸。在本研究中，我们研究了人肝细胞癌（HCC）中PD - Ls的表达，以确定其在根治性手术后的预后意义。
实验设计：采用免疫组织化学方法研究PD - Ls的表达以及颗粒酶B⁺细胞毒性T细胞和FoxP3⁺调节性T细胞在组织芯片上的浸润情况，组织芯片包含240例随机选取的接受手术的HCC患者。结果在另外125例HCC患者的独立队列中进一步验证。通过蛋白质印迹法检测HCC细胞系上PD - Ls的表达。
结果：PD - L1高表达患者的预后明显比低表达患者差。尽管PD - L2高表达患者的生存期也较差，但复发差异无统计学意义。多变量分析确定肿瘤PD - L1表达是术后复发的独立预测因子。未发现PD - Ls表达与颗粒酶B⁺淋巴细胞浸润之间存在相关性，然而发现PD - Ls表达与FoxP3⁺淋巴细胞浸润之间存在显著正相关。此外，肿瘤浸润性细胞毒性T细胞和调节性T细胞也是生存期和复发的独立预后因素。PD - L1表达的预后价值在独立数据集中得到验证。
结论：我们的数据首次表明PD - L1状态可能是HCC患者复发的一个新的预测因子，并为开发针对这种致命恶性肿瘤的靶向PD - L1/PD - 1通路的新疗法提供了理论依据。
Purpose: The aberrant expression of programmed cell death 1 ligands 1 and 2 (PD-Ls) on tumor cells dampens antitumor immunity, resulting in tumor immune evasion, In this study, we investigated the expression of PD-Ls in human hepatocellular carcinoma (HCC) to define their prognostic significance after curative surgery.Experimental Design: Immunohistochemistry was used to investigate PD-Ls expression as well as granzyme B+ cytotoxic and FoxP3(1) regulatory T cell infiltration on tissue microarrays containing 240 randomly selected HCC patients who underwent surgery. The results were further verified in an independent cohort of 125 HCC patients. PD-Ls expression on HCC cell lines was detected by Western blot assay.Results: Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression, Although patients with higher expression of PD-L2 also had a poorer survival, the difference in recurrence was not statistically significant. Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence. No correlation was found between PD-Ls expression and granzyme B+ lymphocyte infiltration, whereas a significant positive correlation was detected between PD-Ls expression and FoxP3(+) lymphocyte infiltration. In addition, tumor-infiltrating cytotoxic and regulatory T cells were also independent prognosticators for both survival and recurrence. The prognostic value of PD-L1 expression was validated in the independent data set.Conclusion: Our data suggest for the first time that PD-L1 status may be a new predictor of recurrence for HCC patients and provide the rationale for developing a novel therapy of targeting the PD-L1/PD-1 pathway against,this fatal malignancy.