PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer.
PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer.
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DOI：
10.1016/j.jtho.2016.09.002
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Hirsch FR
中科院分区：
文献类型：
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作者：
Yu H;Batenchuk C;Badzio A;Boyle TA;Czapiewski P;Chan DC;Lu X;Gao D;Ellison K;Kowalewski AA;Rivard CJ;Dziadziuszko R;Zhou C;Hussein M;Richards D;Wilks S;Monte M;Edenfield W;Goldschmidt J;Page R;Ulrich B;Waterhouse D;Close S;Jassem J;Kulig K;Hirsch FR
针对免疫检查点的治疗性抗体显示出有希望的结果。程序性死亡配体1（PD-L1）是一种免疫检查点配体，通过结合PD-L1受体（程序性死亡1）阻断癌症免疫周期。我们研究了小细胞肺癌中PD-L1蛋白表达和信使RNA（mRNA）水平。使用SP142和Dako 28-8 PD-L1抗体，通过免疫组织化学（IHC）和原位杂交，在原发性肿瘤组织微阵列中测定PD-L1蛋白表达和mRNA水平，肿瘤细胞和肿瘤浸润免疫细胞（TIIC）均来自98例局限性疾病SCLC队列。仅使用Dako 28-8抗体评估了来自广泛性疾病SCLC患者的96份肿瘤标本的额外队列的肿瘤细胞中的PD-L1蛋白表达。肿瘤细胞中PD-L1蛋白表达的总体患病率为16.5%。在局限性疾病队列中，SP142和Dako 28-8组肿瘤细胞中PD-L1蛋白表达的发生率分别为14.7%和19.4%（肿瘤比例评分临界值≥1%），15.5%的肿瘤样本中PD-L1 mRNA ISH表达阳性。PD-L1蛋白/mRNA表达增加与更多TIIC的存在相关（p < 0.05）。广泛疾病队列显示，使用Dako 28-8抗体的肿瘤细胞中PD-L1蛋白表达阳性率为14.9%。SCLC的一个子集的特征在于肿瘤细胞中的阳性PD-L1和/或mRNA表达。PD-L1和mRNA表达水平越高，TIIC浸润越多。PD-L1在SCLC中的患病率低于已发表的NSCLC患病率。PD-L1表达在SCLC治疗中的预测作用仍有待确定。
Therapeutic antibodies to immune checkpoints show promising results. Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD-L1 receptor (programmed death 1). We investigated PD-L1 protein expression and messenger RNA (mRNA) levels in SCLC. PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28-8 PD-L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor-infiltrating immune cells (TIICs) obtained from a limited-disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive-disease SCLC was assessed for PD-L1 protein expression in tumor cells with Dako 28-8 antibody only. The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%. In the limited-disease cohort, the prevalences of PD-L1 protein expression in tumor cells with SP142 and Dako 28-8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD-L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD-L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive-disease cohort demonstrated a 14.9% positivity of PD-L1 protein expression in tumor cells with Dako 28-8 antibody. A subset of SCLCs is characterized by positive PD-L1 and/or mRNA expression in tumor cells. Higher PD-L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD-L1 in SCLC is lower than that published for NSCLC. The predictive role of PD-L1 expression in SCLC treatment remains to be established.