The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma

• DOI: 10.1007/s00262-018-2271-4
• Publication Date: 2018-12-01T16:20:30Z
• Authors: Boyang Chang; Tao Huang; Huajun Wei; Lujun Shen; Duo Zhu; Wenjun He; Qifeng Chen; Huihua Zhang; Yunjian Li; Ruopan Huang; Wang Li; Peihong Wu
• Keywords: Adult; Male; 0301 basic medicine; Carcinoma, Hepatocellular; Liver Neoplasms; Programmed Cell Death 1 Receptor; Middle Aged; Prognosis; B7-H1 Antigen; 3. Good health; 03 medical and health sciences; C-Reactive Protein; Lymphocytes, Tumor-Infiltrating; Humans; Original Article; Female; Aged; Retrospective Studies

Blocking the programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in hepatocellular carcinoma (HCC) is a very promising approach in immunotherapy. However, the correlation and prognostic values of serum soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have not been explored conjointly in HCC patients.This study retrospectively included 120 HCC patients receiving radical resection. The serum levels of sPD-1/sPD-L1 and inflammatory cytokines were measured by antibody array assay. Immunohistochemistry was applied to assess both the expression of membrane-bound PD-L1, and the number of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs.The best cut-off values of sPD-1 and sPD-L1 for predicting disease-free survival (DFS) were 33.0 µg/ml and 11.2 µg/ml, respectively. Multivariable analysis showed that sPD-L1 was a negative independent prognostic factor [DFS, Hazard Ratio (HR) 2.58, 95% CI 1.14-5.84, P = 0.023; overall survival (OS), HR 1.77, 95% CI 1.01-3.12, P = 0.048], while sPD-1 was a favorable independent prognostic factor (DFS, HR 0.32, 95% CI 0.14-0.74, P = 0.007; OS, HR 0.54, 95% CI 0.30-0.98, P = 0.044) in HCC patients. We also observed some similar associations between inflammatory cytokines (IL-10, IL-17, TNF-α) and sPD-1 or sPD-L1, as well as a close positive association between sPD-1 and sPD-L1. No significant associations of sPD-1/sPD-L1 with either intra-tumoral PD-L1 expression, or the numbers of CD4+ TILs and CD8+ TILs were determined.Our findings indicate that sPD-1 and sPD-L1 are independent prognostic factors with opposite prognostic roles in predicting both DFS and OS in HCC patients.