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人癌症中程序性死亡受体配体1(PD-L1)的表达及其与临床结局的关联。

PD-L1 expression in human cancers and its association with clinical outcomes.

作者信息

Wang Xin, Teng Feifei, Kong Li, Yu Jinming

机构信息

School of Medicine and Life Sciences, University of Jinan - Shandong Academy of Medical Sciences; Department of Radiation Oncology, Shandong Cancer Hospital and Institute.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute; School of Medicine, Shandong University, Jinan, People's Republic of China.

出版信息

Onco Targets Ther. 2016 Aug 12;9:5023-39. doi: 10.2147/OTT.S105862. eCollection 2016.

Abstract

PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial. Blocking antibodies that target PD-1 and PD-L1 have achieved remarkable response rates in cancer patients who have PD-L1-overexpressing tumors. However, using PD-L1 as an exclusive predictive biomarker for cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. Factors that affect the accuracy of PD-L1 immunohistochemistry staining are as follows. First, antibodies used in different studies have different sensitivity. Second, in different studies, the cut-off value of PD-L1 staining positivity is different. Third, PD-L1 expression in tumors is not uniform, and sampling time and location may affect the results of PD-L1 staining. Therefore, better understanding of tumor microenvironment and use of other biomarkers such as gene marker and combined index are necessary to better identify patients who will benefit from PD-1/PD-L1 checkpoint blockade therapy.

摘要

程序性死亡配体1(PD-L1)是一种免疫抑制分子,可抑制T细胞的激活,导致肿瘤进展。在胃癌、肝细胞癌、肾细胞癌、食管癌、胰腺癌、卵巢癌和膀胱癌等癌症中,PD-L1的过表达与不良临床结局相关。相比之下,PD-L1表达与乳腺癌和默克尔细胞癌较好的临床结局相关。PD-L1表达在肺癌、结直肠癌和黑色素瘤中的预后价值存在争议。靶向程序性死亡受体1(PD-1)和PD-L1的阻断抗体在患有PD-L1过表达肿瘤的癌症患者中取得了显著的缓解率。然而,由于PD-L1免疫组化染色的准确性较低,将PD-L1用作癌症免疫治疗的唯一预测生物标志物存在疑问。影响PD-L1免疫组化染色准确性的因素如下。首先,不同研究中使用的抗体具有不同的敏感性。其次,在不同研究中,PD-L1染色阳性的临界值不同。第三,肿瘤中PD-L1的表达不均匀,采样时间和位置可能影响PD-L1染色结果。因此,为了更好地识别将从PD-1/PD-L1检查点阻断治疗中获益的患者,有必要更好地了解肿瘤微环境并使用其他生物标志物,如基因标志物和联合指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a83f/4990391/9e39ad287393/ott-9-5023Fig1.jpg

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