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针对肾细胞癌的 PD-1/PD-L1 通路。

Targeting the PD-1/PD-L1 Pathway in Renal Cell Carcinoma.

机构信息

Department of Pathology, University Hospital, 35000 Rennes, France.

Université Rennes, Inserm, EHESP (Ecole des Hautes Etudes en Santé Publique), Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.

出版信息

Int J Mol Sci. 2019 Apr 4;20(7):1692. doi: 10.3390/ijms20071692.

Abstract

Renal cell carcinoma encompass distinct diseases with different pathologic features and distinct molecular pathways. Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway alone or in combination have greatly changed clinical management of metastatic renal cell carcinoma, now competing with antiangiogenic drugs in monotherapy for first-line treatment. However, long-term response rates are low, and biomarkers are needed to predict treatment response. Quantification of PD-L1 expression by immunohistochemistry was developed as a promising biomarker in clinical trials, but with many limitations (different antibodies, tumour heterogeneity, specimens, and different thresholds of positivity). Other biomarkers, including tumour mutational burden and molecular signatures, are also developed and discussed in this review.

摘要

肾细胞癌包含具有不同病理特征和不同分子途径的不同疾病。单独或联合使用针对程序性死亡受体配体 1(PD-L1)/程序性死亡受体 1(PD-1)途径的免疫检查点抑制剂极大地改变了转移性肾细胞癌的临床治疗方法,现在与抗血管生成药物竞争一线治疗。然而,长期反应率较低,需要生物标志物来预测治疗反应。免疫组织化学检测 PD-L1 表达的定量分析作为一种很有前途的生物标志物在临床试验中得到了发展,但存在许多局限性(不同的抗体、肿瘤异质性、标本和不同的阳性阈值)。在本综述中还讨论了其他生物标志物,包括肿瘤突变负担和分子特征。

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