Table_1_Prognostic significance of programmed cell death ligand 1 blood markers in non-small cell lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis.docx

BackgroundImmune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1 (PD-L1) in peripheral blood, including soluble form (sPD-L1), expression on circulating tumor cells (CTCs PD-L1) and exosomes (exoPD-L1), are minimally invasive and promising markers for patient selection and management, but their prognostic significance remains inconclusive. Here, we performed a meta-analysis for the prognostic value of PD-L1 blood markers in NSCLC patients treated with ICIs.
MethodsEligible studies were obtained by searching PubMed, EMBAS, Web of Science, and Cochrane Library prior to November 30, 2023. The associations between pre-treatment, post-treatment and dynamic changes of blood PD-L1 levels and progression-free survival (PFS)/over survival (OS) were analyzed by estimating hazard ratio (HR) and 95% confidence interval (CI).
ResultsA total of 26 studies comprising 1606 patients were included. High pre- or post-treatment sPD-L1 levels were significantly associated with worse PFS (pre-treatment: HR=1.49, 95%CI 1.13–1.95; post-treatment: HR=2.09, 95%CI 1.40–3.12) and OS (pre-treatment: HR=1.83, 95%CI 1.25–2.67; post-treatment: HR=2.60, 95%CI 1.09–6.20, P=0.032). High pre-treatment exoPD-L1 levels predicted a worse PFS (HR=4.24, 95%CI 2.82–6.38, P<0.001). Pre-treatment PD-L1+ CTCs tended to be correlated with prolonged PFS (HR=0.63, 95%CI 0.39–1.02) and OS (HR=0.58, 95%CI 0.36–0.93). Patients with up-regulated exoPD-L1 levels, but not sPD-L1, after ICIs treatment had significantly favorable PFS (HR=0.36, 95%CI 0.23–0.55) and OS (HR=0.24, 95%CI 0.08–0.68).
ConclusionPD-L1 blood markers, including sPD-L1, CTCs PD-L1 and exoPD-L1, can effectively predict prognosis, and may be potentially utilized for patient selection and treatment management for NSCLC patients receiving ICIs.

背景
免疫检查点抑制剂（Immune checkpoint inhibitors, ICIs）对非小细胞肺癌（non-small cell lung cancer, NSCLC）的治疗具有明确疗效，但整体应答率仍偏低。外周血中的程序性死亡配体1（Programmed cell death ligand 1, PD-L1）相关标志物涵盖可溶性形式（soluble form, sPD-L1）、循环肿瘤细胞表面表达的PD-L1（circulating tumor cells PD-L1, CTCs PD-L1）以及外泌体携带的PD-L1（exosomes PD-L1, exoPD-L1），此类标志物具备微创性优势，是用于患者筛选与临床管理的颇具前景的候选标志物，但其预后预测价值目前尚未达成共识。本研究针对接受免疫检查点抑制剂治疗的非小细胞肺癌患者，开展了一项关于血液PD-L1标志物预后价值的荟萃分析。
方法
通过检索PubMed、EMBASE、Web of Science及Cochrane Library数据库（检索时限截至2023年11月30日），筛选符合纳入标准的相关研究。通过估算风险比（hazard ratio, HR）与95%置信区间（confidence interval, CI），分析治疗前、治疗后血液PD-L1水平及其动态变化与无进展生存期（progression-free survival, PFS）、总生存期（overall survival, OS）之间的关联。
结果
本研究共纳入26项相关研究，累计涉及1606例患者。治疗前或治疗后高可溶性PD-L1（sPD-L1）水平均与更差的无进展生存期（治疗前：HR=1.49, 95%CI 1.13–1.95；治疗后：HR=2.09, 95%CI 1.40–3.12）及总生存期（治疗前：HR=1.83, 95%CI 1.25–2.67；治疗后：HR=2.60, 95%CI 1.09–6.20, P=0.032）显著相关。治疗前高外泌体PD-L1（exoPD-L1）水平可预测更差的无进展生存期（HR=4.24, 95%CI 2.82–6.38, P<0.001）。治疗前PD-L1阳性循环肿瘤细胞（PD-L1+ CTCs）倾向于与更长的无进展生存期（HR=0.63, 95%CI 0.39–1.02）及总生存期（HR=0.58, 95%CI 0.36–0.93）相关。接受免疫检查点抑制剂治疗后，外泌体PD-L1水平上调（而非可溶性PD-L1水平上调）的患者，其无进展生存期（HR=0.36, 95%CI 0.23–0.55）及总生存期（HR=0.24, 95%CI 0.08–0.68）显著更优。
结论
血液PD-L1标志物，包括可溶性PD-L1、循环肿瘤细胞PD-L1及外泌体PD-L1，可有效预测患者预后，有望用于接受免疫检查点抑制剂治疗的非小细胞肺癌患者的筛选与治疗管理。