Characteristics of Soluble PD-L1 and PD-1 Expression and Their Correlations With Immune Status and Prognosis in Advanced Lung Cancer

Ran Li; Hongge Liang; Ying Shang; Zhengwu Yang; Keqiang Wang; Donghong Yang; Jing Bao; Wen Xi; Dexun Zhou; Wentao Ni; Zhancheng Gao; Xinlin Mu

doi:10.1111/ajco.14145

Characteristics of Soluble PD-L1 and PD-1 Expression and Their Correlations With Immune Status and Prognosis in Advanced Lung Cancer

Asia Pac J Clin Oncol. 2025 Jan 4. doi: 10.1111/ajco.14145. Online ahead of print.

Authors

Ran Li^{1

2}, Hongge Liang^{1

2

3}, Ying Shang^{1

2}, Zhengwu Yang^{1

2}, Keqiang Wang^{1

2}, Donghong Yang^{1

2}, Jing Bao^{1

2}, Wen Xi^{1

2}, Dexun Zhou^{1

2}, Wentao Ni^{1

2}, Zhancheng Gao^{1

2}, Xinlin Mu^{1

2}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China.
² Lung Cancer Center, Peking University People's Hospital, Beijing, China.
³ Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

PMID: 39754708
DOI: 10.1111/ajco.14145

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: lung cancer; lymphocyte subsets; prognosis; soluble PD‐1; soluble PD‐L1.