Comparative analysis of programmed cell death ligand 1 assays in renal cell carcinoma
Comparative analysis of programmed cell death ligand 1 assays in renal cell carcinoma
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DOI：
10.1111/his.14054
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发表时间：
2020-06-07
期刊：
影响因子：
6.4
通讯作者：
Lee, Sang Eun
中科院分区：
文献类型：
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作者：
Lee, Kyu Sang;Choe, Gheeyoung;Lee, Sang Eun
目的程序性细胞死亡配体1(PD-L1)的表达在肾癌PD-L1靶向治疗的临床试验中的重要性已经显现。方法和结果美国食品和药物管理局批准的两种PD-L1检测方法(22C3和SP142)和一种仅供研究使用的抗体(E1L3N)用于591例肾癌患者的回顾性队列研究。测定肿瘤细胞(TCS)、免疫细胞(ICs)PD-L1阳性细胞数和联合阳性积分(CPS)。用22C3、SP142和E1L3N检测，PD-L1在TCS和Gt；=1%的病例中阳性表达分别为24例(4.1%)、12例(2.0%)和16例(2.7%)，在IC&Gt；=1%的病例中分别为132例(22.3%)、120例(20.3%)和65例(11.0%)。PD-L1在三种检测方法中的表达积分呈中高度正相关(Rho=0.599~0.835，P<；0.001)。虽然E1L3N在ICs中的染色频率相对较低，但检测结果类似。22C3在TCS中呈频繁阳性。PD-L1在TCS上的表达与乳头状2型肾癌相关(P<；0.001)。IC的浸润和PD-L1在ICs上的表达主要见于透明细胞和乳头状肾细胞癌(P<；0.05)。结论程序性死亡1(PD-1)/PD-L1靶向治疗对乳头状肾细胞癌患者可能是有益的，即使他们被归类为异质性组。PD-L1检测应谨慎选择，在决定PD-L1检测之前，需要对肾癌进行准确的组织学分型，因为在不同的肾癌亚型中观察到不同的PD-L1表达。
Aims The importance of programmed cell death ligand 1 (PD-L1) expression has emerged in clinical trials of PD-L1 target therapy in renal cell carcinoma (RCC). This study compares PD-L1 assays in RCC.Methods and results Two US Food and Drug Administration-approved PD-L1 assays (22C3 and SP142) and one research-use only antibody (E1L3N) were used in a retrospective cohort of 591 patients with RCC. PD-L1 positivity on tumour cells (TCs) and immune cells (ICs) and combined positive score (CPS) were evaluated. With the 22C3, SP142 and E1L3N assays, positive PD-L1 expression on TCs >= 1% was observed in 24 (4.1%), 12 (2.0%) and 16 (2.7%) cases and on ICs >= 1% was observed in 132 (22.3%), 120 (20.3%) and 65 (11.0%) cases, respectively. PD-L1 expression scores among the three assays showed moderate-high positive correlation (rho = 0.599-0.835, P < 0.001). Assays appeared similar, although staining in ICs was comparatively less frequent with E1L3N. 22C3 showed frequent positivity in TCs. PD-L1 expression on TCs was associated with papillary type 2 RCC (P < 0.001). IC infiltration and PD-L1 expression on ICs were predominantly found in clear cell and papillary type 1 RCC (P < 0.05).Conclusions Programmed death 1 (PD-1)/PD-L1 target therapy may be beneficial for patients with papillary type 2 RCC, even if they are categorised as a heterogeneous group. PD-L1 assays should be carefully selected, and accurate histological subtyping of RCC is needed prior to decisions on PD-L1 testing, because of the different PD-L1 expression observed among varying RCC subtypes.