Li Ran, Liang Hongge, Shang Ying, Yang Zhengwu, Wang Keqiang, Yang Donghong, Bao Jing, Xi Wen, Zhou Dexun, Ni Wentao, Gao Zhancheng, Mu Xinlin
Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China.
Lung Cancer Center, Peking University People's Hospital, Beijing, China.
Asia Pac J Clin Oncol. 2025 Jan 4. doi: 10.1111/ajco.14145.
Our study aims to evaluate the characteristics of serum soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) levels and their correlations with immune status and prognosis in advanced lung cancer patients.
Patients diagnosed with advanced lung cancer based on histology or cytology in Peking University People's Hospital from July 2020 to November 2021 were enrolled. Clinicopathological data were recorded and analyzed. Treatment efficacy was evaluated according to RESIST 1.1 criteria. The serum levels of sPD-L1 and sPD-1 were detected by enzyme-linked immunosorbent assay (ELISA). Lymphocyte subsets were measured by flow cytometry to evaluate the immune status of the patients.
A total of 65 patients with advanced lung cancer were enrolled. sPD-L1 level in lung cancer patients (15.67 ± 11.09 pg/mL, p = 0.001) was significantly higher than those in healthy controls (5.21 ± 4.46 pg/mL). sPD-1 level did not show a significant difference between patients with lung cancer and healthy controls. sPD-L1 level in patients with progressive disease (PD) was significantly higher than those with partial response (PR) (20.94 ± 8.91 vs. 13.14 ± 12.66 pg/mL, p = 0.033). In treatment-naïve patients, sPD-L1 level was negatively correlated with the lymphocyte ratio (correlation coefficient = -0.452, p = 0.014). Kaplan-Meier survival analysis showed that patients with low sPD-L1 level had a significantly longer progression-free survival (PFS) (10.4 vs. 5.7 months, p = 0.023). However, sPD-1 level did not correlate with lymphocyte subsets or prognosis in overall patients with lung cancer. Subgroup analysis showed that prolonged PFS in patients with low sPD-L1 level was exclusively shown in the NSCLC subgroup, not in the SCLC subgroup. In the subgroups of patients who subsequently received immunotherapy, low sPD-L1 level was correlated with longer PFS in the overall patients and NSCLC patients, and low sPD-1 level was correlated with longer PFS exclusively in NSCLC patients.
Serum sPD-L1 level was higher in patients with advanced lung cancer than healthy individuals, which was negatively correlated with the proportion of lymphocytes and prognosis. Serum sPD-1 level did not show significant difference between patients with lung cancer and healthy individuals, which showed no correlation with lymphocyte subsets and the prognosis of overall patients, except NSCLC patients receiving immunotherapy.
本研究旨在评估晚期肺癌患者血清可溶性程序性死亡受体1（sPD-1）和可溶性程序性死亡配体1（sPD-L1）水平的特征及其与免疫状态和预后的相关性。
纳入2020年7月至2021年11月在北京大学人民医院根据组织学或细胞学诊断为晚期肺癌的患者。记录并分析临床病理数据。根据RESIST 1.1标准评估治疗疗效。采用酶联免疫吸附测定（ELISA）检测血清sPD-L1和sPD-1水平。通过流式细胞术检测淋巴细胞亚群以评估患者的免疫状态。
共纳入65例晚期肺癌患者。肺癌患者的sPD-L1水平（15.67±11.09 pg/mL，p = 0.001）显著高于健康对照者（5.21±4.46 pg/mL）。肺癌患者与健康对照者的sPD-1水平无显著差异。疾病进展（PD）患者的sPD-L1水平显著高于部分缓解（PR）患者（20.94±8.91 vs. 13.14±12.66 pg/mL，p = 0.033）。在未经治疗的患者中，sPD-L1水平与淋巴细胞比例呈负相关（相关系数 = -0.452，p = 0.014）。Kaplan-Meier生存分析显示，sPD-L1水平低的患者无进展生存期（PFS）显著更长（10.4 vs. 5.7个月，p = 0.023）。然而，sPD-1水平与肺癌总体患者的淋巴细胞亚群或预后无关。亚组分析显示，sPD-L1水平低的患者PFS延长仅在非小细胞肺癌（NSCLC）亚组中出现，而在小细胞肺癌（SCLC）亚组中未出现。在随后接受免疫治疗的患者亚组中，sPD-L1水平低与总体患者和NSCLC患者的PFS延长相关，而sPD-1水平低仅与NSCLC患者的PFS延长相关。
晚期肺癌患者血清sPD-L1水平高于健康个体，且与淋巴细胞比例及预后呈负相关。肺癌患者与健康个体的血清sPD-1水平无显著差异，且除接受免疫治疗的NSCLC患者外，sPD-1水平与淋巴细胞亚群及总体患者预后无关。
