目的：观察扶正方药对晚期三线非小细胞肺癌（NSCLC）患者外周血中12 种可溶性免疫检查点分子水平的影响，并分析可溶性免疫检查点基线水平与NSCLC患者无进展生存期（PFS）的关系。方法：纳入2020 年10月至2023 年4月在龙华医院肿瘤科接受三线治疗（扶正方药联合标准西医方案治疗）的72例晚期NSCLC患者，采用LEGENDplex ?多因子试剂盒检测患者治疗前及治疗4 疗程后可溶性免疫检查点分子的表达水平，分析基线水平与 PFS 预后的相关性。结果：治疗4 个疗程后，sCD137、sTGF-β1、sPD-L1、sPD-L2等指标均明显下降（P<0.05 或P<0.01），Kaplan-Meier 生存分析表明sPD-L2高水平患者的PFS短于sPD-L2低水平患者的PFS（P<0.05），COX 多因素分析表明sPD-L2 水平是晚期三线NSCLC 患者PFS 的独立影响因子（P<0.05）。结论：扶正方药对外周血可溶性免疫检查点蛋白表达具有一定的调节作用，高水平的sPD-L2预示晚期NSCLC患者较短的PFS，sPD-L2可能是晚期三线治疗NSCLC患者PFS的独立影响因子。

Objective: To observe the effect of Fuzheng formulas on the peripheral blood levels of 12 soluble immune checkpoint molecules in patients with advanced non-small cell lung cancer (NSCLC) treated with third-line therapy, and to analyze the relationship between the baseline level of soluble immune checkpoints and the progression-free survival (PFS) of NSCLC patients. Methods: A total of 72 patients with advanced NSCLC who received third-line treatment (Fuzheng formulas combined with standard Western medicine treatment regimen) in the Department of Oncology, Longhua Hospital from October 2020 to April 2023 were enrolled. The LEGENDplexTM multi-factor kit was used to detect the expression level of soluble immune checkpoint molecules before and after 4 cycles of treatment, and the correlation between their baseline levels and PFS prognosis was analyzed. Results: After 4 cycles of treatment, sCD137, sTGF- β1, sPD-L1, sPD-L2 and other indicators were significantly decreased (P<0.05 or P<0.01). Kaplan-Meier survival analysis showed that the PFS of patients with high sPD-L2 level was shorter than that of patients with low sPD-L2 level (P<0.05). COX multivariate analysis showed that sPD-L2 expression level was an independent impact factor for PFS in advanced NSCLC patients treated with third-line therapy (P<0.05). Conclusion: Fuzheng formulas have a certain regulatory effect on the levels of soluble immune checkpoint molecules. A high level of sPD-L2 indicates shorter PFS in patients with advanced NSCLC, and sPD-L2 may be an independent impact factor for PFS in advanced NSCLC patients undergoing third-line treatment.

国家自然科学基金（No. 82374533）；上海市自然科学基金项目（No. 21ZR1463700）；上海市卫生健康委员会卫生行业临床研究专项（No. 202140370）