Dataset Information

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.

ABSTRACT:

Background

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.

Methods

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.

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. 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.

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.

SUBMITTER: Chang B

PROVIDER: S-EPMC6426820 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

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.

Chang Boyang B Huang Tao T Wei Huajun H Shen Lujun L Zhu Duo D He Wenjun W Chen Qifeng Q Zhang Huihua H Li Yunjian Y Huang Ruopan R Li Wang W Wu Peihong P

Cancer immunology, immunotherapy : CII 20181201 3

<h4>Background</h4>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.<h4>Methods</h4>This study retrospectively included 120 HCC patients receiving radical resection. The serum levels of sPD-1/sPD-L1 and inflammatory cytokines were meas ...[more]

PMID: 30506460

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Project description:Background: Soluble PD-L1 (sPD-L1) in the circulation has been documented to activate global immunosuppression and is considered a predictor of negative clinical outcomes in several malignances. However, the clinical significance of sPD-L1 in the peripheral blood and cerebrospinal fluid (CSF) of patients with glioma remains unclear. Objective: The aim of this study was to detect the correlations of sPD-L1 with clinical features in brain tumors and assess the diagnostic value of this protein in gliomas. Methods: Serum samples were obtained from 73 patients with glioma, 20 patients with meningioma, and 49 healthy controls (HCs) in this study. In total, 31 CSF samples were collected from the matched glioma patients, and seven samples were collected from the matched meningioma patients. The expression of serum sPD-L1 in the glioma cohort was followed for 20 days after surgery to examine the kinetics in the circulation. Inflammatory markers were evaluated based on preoperative blood parameters. The sPD-L1 levels in the serum and CSF were determined by enzyme-linked immunosorbent assay (ELISA). The logistic regression model was used to assess the independent associations of sPD-L1 with gliomas, including high-grade gliomas. Results: Serum and CSF levels of sPD-L1 were significantly elevated in patients with gliomas compared to those with meningiomas and HCs. Additionally, increased levels of sPD-L1 were observed in relatively advanced tumors. sPD-L1 overexpression in the CSF appears to be more representative of aggressive tumor features than overexpression in the serum. For glioma diagnosis, both serum and CSF sPD-L1 showed significant value in the diagnosis and stratification of glioma, and the best diagnostic performance was obtained with serum sPD-L1 rather than blood-based inflammatory markers. In addition, a descending trend in the level of serum sPD-L1 was observed in postoperative patients. Conclusion: In gliomas, elevated circulating and CSF sPD-L1 levels are associated with aggressive biological activities. The results of the current study suggest that sPD-L1 is a promising biomarker for gliomas that can be used in clinical practice.

Project description:BACKGROUND:The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications. METHODS:Sixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue. RESULTS:The median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels (r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001). CONCLUSIONS:Serum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients. TRIAL REGISTRATION:The study population was patients who were diagnosed with PCNSL between January 2009 and February 2017 and registered for our prospective cohort studies after providing written informed consent (ClinicalTrials.gov: NCT00822731 [date of registration - January 14, 2009] and NCT01877109 [date of registration - June 13, 2013]).

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Project description:Accumulating evidence suggests that regulatory B cells (Bregs) play important roles in inhibiting the immune response in tumors. Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) are important molecules that maintain the balance of the immune response and immune tolerance. This study aims to evaluate the soluble form of PD-L1 and its function in inducing the differentiation of B lymphocytes, investigate the relationship between soluble PD-L1 (sPD-L1) and B-cell subsets, and explore the antitumor activity of T lymphocytes after PD-L1 blockade in coculture systems. In an effort to explore the role of sPD-L1 in human breast cancer etiology, we examined the levels of sPD-L1 and interleukin-10 (IL-10) in the serum of breast tumor patients and the proportions of B cells, PD-1+ B cells, Bregs, and PD-1+ Bregs in the peripheral blood of patients with breast tumors and assessed their relationship among sPD-L1, IL-10, and B-cell subsets. The levels of sPD-L1 and IL-10 in serum were found to be significantly higher in invasive breast cancer (IBCa) patients than in breast fibroadenoma (FIBma) patients. Meanwhile, the proportions and absolute numbers of Bregs and PD-1+ Bregs in the peripheral blood of IBCa patients were significantly higher than those of FIBma patients. Notably, they were the highest in triple-negative breast cancer (TNBC) among other subtypes of IBCa. Positive correlations of sPD-L1 and IL-10, IL-10 and PD-1+ Bregs, and also sPD-L1 and PD-1+ Bregs were observed in IBCa. We further demonstrated that sPD-L1 could induce Breg differentiation, IL-10 secretion, and IL-10 mRNA expression in a dose-dependent manner in vitro. Finally, the induction of regulatory T cells (Tregs) by Bregs was further shown to suppress the antitumor response and that PD-L1 blockade therapies could promote the apoptosis of tumor cells. Together, these results indicated that sPD-L1 could mediate the differentiation of Bregs, expand CD4+ Tregs and weaken the antitumor activity of CD4+ T cells. PD-L1/PD-1 blockade therapies might be a powerful therapeutic strategy for IBCa patients, particularly for TNBC patients with high level of PD-1+ Bregs.

Dataset Information

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.

Background

Methods

Results

Conclusions

Publications

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.

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