循环肿瘤细胞数量及其PD-L1表达水平指导PD-1单抗个体化治疗食管鳞癌的研究

PD-1单抗是新型的抗肿瘤免疫抑制剂。存在的问题是缺乏预测疗效的标志物。目前探讨肿瘤微卫星状态、突变负荷（TMB）或PD-L1表达预测疗效的研究较多，但是除了肿瘤错配修复基因缺陷（dMMR）/微卫星不稳定性（MSI）能找到5%的患者外，其他标志物尚不能预测消化系统等肿瘤的疗效。循环肿瘤细胞（CTCs）作为新型标志物，证明可监测肿瘤的疗效。本课题组创建了多肽纳米磁珠捕获CTCs方法，和免疫荧光法对CTCs的PD-L1表达定量分级的评价体系，并在小样本的研究中显示了很好的疗效预测苗头。这个新的肿瘤标志物是否能有效预测PD-1单抗疗效呢?本研究拟利用PD-1单抗治疗食管癌的多中心临床研究，系统评价PD-1单抗治疗前及用药过程中CTCs数量及PD-L1表达，并与肿瘤dMMR/MSI、TMB及PD-L1表达进行比较，验证CTCs数目及其PD-L1表达在预测和动态监测PD-1单抗疗效的价值。

Anti-programmed death1 (PD-1) is a new immune checkpoint inhibitor for cancer treatment. The main problem is the lack of biomarkers for predicting efficacy. There are numerous studies toinvestigate the predictive value of biomarkers for drug efficacy, such as microsatellite status, tumor mutation burden (TMB) and PD-L1 expression in tumor tissues. However, mismatch repair deficient (dMMR)/microsatellite instability (MSI) can only find in 5% patients, while TMB and PD-L1 expression in tumor tissues could not predict response in multitumors including digestive tract cancers. As a biomarker of liquid biopsy, circulating tumor cells (CTCs) have been used asresponseand prognostic prediction insome solid tumors. Our team has established Pep@MNPs isolated system for enumerating CTCs and a grading system for detecting the expression of PD-L1 in CTCs by immunofluorescence and quantitative fluorescence, which showed a good predictive value in two pilot clinical study of solid tumors. This study aims to systematically evaluate the CTCs number and the expression of PD-L1 on CTCs of esophageal squamous carcinoma patients before and during the treatment of PD-1 monoclonal antibody by using the multi-center clinical trials. In order to realize individual anti-PD-1 antibody therapy, this study is to determine the predictive value of dynamic changes of CTCs number, the expression level of PD-L1 on CTCs before and after treatment on the efficacy of PD-1 monoclonal antibody for esophageal squamous carcinoma patients by comparing with that of dMMR/MSI, TMB and the PD-L1 expression in tumor tissues.