Li Yue, Li Chong, Jiang Ya, Han Xue, Liu Sisi, Xu Xiuxiu, Tang Wanxiangfu, Ou Qiuxiang, Bao Hua, Wu Xue, Shao Yang, Xing Minyan, Zhang Yixiang, Wang Yuezhen
Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150081 Harbin, Heilongjiang, China.
Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
J Oncol. 2022 Apr 11;2022:1763778. doi: 10.1155/2022/1763778. eCollection 2022.
Programmed cell death 1 ligand 1 (PD-L1) has been approved as predictive biomarker for non-small-cell lung cancer (NSCLC) patients treated with PD-(L)1 blockade therapy. The clinical/genomic features associated with PD-L1 are not well studied. Genomic profiling of tumor biopsies from 883 Chinese NSCLC patients was performed by targeted next-generation sequencing. Immunohistochemical analysis was conducted to evaluate PD-L1 expression levels using antibodies Dako 22C3 and 28-8, respectively. Our study showed distinct correlation between PD-L1 expression and clinical/genomic characteristics when using different PD-L1 antibodies and in different histological subtypes including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively. PD-L1 high expression (22C3) was associated with male and lymph node metastasis only in ADC patients. Furthermore, mutations of and , fusion, copy number gains of and , and arm-level amplifications of chr.12p were significantly associated with PD-L1 positive status in ADC patients. For SCC patients, the gain of and and loss of were negatively associated with PD-L1 expression. We also compared our results with other studies and found conflicting results presumably because of the multiplicity of antibody clones and platforms, the difference of cutoffs for assigning PD-L1 expression levels, and the variation in study populations. Our study can help to understand the utility and validity of PD-L1 as biomarker of response to immune checkpoint inhibitors.
程序性细胞死亡1配体1(PD-L1)已被批准作为接受PD-(L)1阻断疗法的非小细胞肺癌(NSCLC)患者的预测生物标志物。与PD-L1相关的临床/基因组特征尚未得到充分研究。通过靶向新一代测序对883例中国NSCLC患者的肿瘤活检组织进行基因组分析。分别使用抗体Dako 22C3和28-8进行免疫组织化学分析,以评估PD-L1表达水平。我们的研究表明,在使用不同的PD-L1抗体时,以及在不同的组织学亚型(包括腺癌(ADC)和鳞状细胞癌(SCC))中,PD-L1表达与临床/基因组特征之间存在明显的相关性。仅在ADC患者中,PD-L1高表达(22C3)与男性和淋巴结转移相关。此外,在ADC患者中, 和 的突变、 融合、 和 的拷贝数增加以及12号染色体短臂的臂水平扩增与PD-L1阳性状态显著相关。对于SCC患者, 和 的增加以及 的缺失与PD-L1表达呈负相关。我们还将我们的结果与其他研究进行了比较,发现结果相互矛盾,这可能是由于抗体克隆和平台的多样性、PD-L1表达水平赋值的临界值差异以及研究人群的差异。我们的研究有助于理解PD-L1作为免疫检查点抑制剂反应生物标志物的效用和有效性。