Abstract
BackgroundBlocking 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.MethodsThis 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.ResultsThe 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.ConclusionsOur 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.
Highlights
Hepatocellular carcinoma (HCC) is the 6th most common cancer and the second leading cause of cancer-related deaths worldwide [1]
Cancer Immunology, Immunotherapy (2019) 68:353–363 significantly improved over the last decade due to the progress in resection criteria and locoregional treatment techniques, more than half of early hepatocellular carcinoma (HCC) patients will suffer from recurrence within 5 years after resection; the majority of recurrences develop within the first year after resection [2]
The serum level of sPD-1 was detectable in all patients, while that of sPD-L1 was below the lower detection limit in 34 (28.3%) cases
Summary
Hepatocellular carcinoma (HCC) is the 6th most common cancer and the second leading cause of cancer-related deaths worldwide [1]. Increasing evidence suggests that cancer immune suppression and immune escape play essential roles in tumor progression. Among these processes, the activation of the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway was identified as the most critical mechanism of tumor evasion, inhibiting T-cell proliferation, inducing T-cell exhaustion and enhancing the activity of regulatory T cells [3]. 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. Results 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. 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. Conclusions 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
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