Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Kruger S
PROVIDER: S-EPMC5467983 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: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.
| S-EPMC6426820 | biostudies-literature
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]).
| S-EPMC7020571 | biostudies-literature
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.
| S-EPMC6989542 | biostudies-literature
Project description:Upon T-cell receptor stimulation, the Programmed cell Death-1 receptor (PD-1) expressed on T-cells can interact with its ligand PD-L1 expressed at the surface of cancer cells or antigen-presenting cells. Monoclonal antibodies targeting PD-1 or PD-L1 are routinely used for the treatment of cancers, but their clinical efficacy varies largely across the variety of tumor types. A part of the variability is linked to the existence of several forms of PD-L1, either expressed on the plasma membrane (mPD-L1), at the surface of secreted cellular exosomes (exoPD-L1), in cell nuclei (nPD-L1), or as a circulating, soluble protein (sPD-L1). Here, we have reviewed the different origins and roles of sPD-L1 in humans to highlight the biochemical and functional heterogeneity of the soluble protein. sPD-L1 isoforms can be generated essentially by two non-exclusive processes: (i) proteolysis of m/exoPD-L1 by metalloproteases, such as metalloproteinases (MMP) and A disintegrin and metalloproteases (ADAM), which are capable of shedding membrane PD-L1 to release an active soluble form, and (ii) the alternative splicing of PD-L1 pre-mRNA, leading in some cases to the release of sPD-L1 protein isoforms lacking the transmembrane domain. The expression and secretion of sPD-L1 have been observed in a large variety of pathologies, well beyond cancer, notably in different pulmonary diseases, chronic inflammatory and autoimmune disorders, and viral diseases. The expression and role of sPD-L1 during pregnancy are also evoked. The structural heterogeneity of sPD-L1 proteins, and associated functional/cellular plurality, should be kept in mind when considering sPD-L1 as a biomarker or as a drug target. The membrane, exosomal and soluble forms of PD-L1 are all integral parts of the highly dynamic PD-1/PD-L1 signaling pathway, essential for immune-tolerance or immune-escape.
| S-EPMC8233757 | biostudies-literature
Project description:IntroductionProgrammed death 1 (PD-1)/programmed death-ligand 1 (PD-L1)-targeted immunotherapies have become a new mode of treatment for several tumours; however, there is limited evidence on the expression and prognostic value of PD-1/PD-L1 in prostate cancer, especially in African men.MethodsPlasma concentrations of PD-L1/PD-1 were assessed using enzyme-linked immunosorbent assay in patients with prostate cancer and normal healthy controls at the Uganda Cancer Institute. The associations between plasma PD-L1/PD-1 concentration levels and serum prostate-specific antigen (PSA) levels, Gleason scores, age, and body mass index (BMI) were determined.ResultsWe found significant differences in the median plasma concentrations of PD-L1 and PD-1 immune checkpoint molecules between prostate cancer cases and normal healthy controls of 0.285 vs 0.035 (p = 0.001) and 0.596 vs 0.355 (p = 0.017), respectively. We found no significant association between age, serum PSA levels, BMI and Gleason scores, and PD-1 among patients with prostate cancer and controls. However, elevated levels of PD-L1 were significantly associated with higher Gleason scores among patients with prostate cancer (p = 0.014).ConclusionsElevated PD-L1 levels were statistically significantly linked to high Gleason scores. These results may guide clinicians in assessing the prognosis of patients individually and selecting patients who will be suitable candidates for anti-PD-L1 immunotherapy.
| S-EPMC9098749 | biostudies-literature
Project description:Introduction: Response to platinum-based therapy is a major prognostic factor in epithelial ovarian cancer (EOC) and reliable prognostic biomarkers are urgently needed to identify patients at high risk. Since ligands of the Programmed Death Receptor-1 (PD-L1 and PD-L2) play a crucial role within the tumor microenvironment for tumorigenesis, we investigated levels of sPD-L1 and sPD-L2 in liquid biopsies of serum samples, and correlated the results with the clinical status, presence of circulating tumor cells (CTCs) and disease outcome in primary EOC patients. Methods: sPD-L1 and sPD-L2 were determined by ELISA in patients (N = 83) and healthy females (N = 29). Gene expression analysis of EpCAM, MUC-1, CA-125, and ERCC1 was performed by RT-PCR after CTCs enrichment. Results: sPD-L1 was significantly (p = 0.0001) increased and sPD-L2 decreased (p = 0.003) in EOC patients compared to controls. While enhanced sPD-L1 was associated with residual tumor burden (p = 0.022), reduced sPD-L2 levels were related to platinum-resistance (p < 0.01) and the presence of ERCC1+ CTCs (p < 0.0001). High sPD-L1 levels were associated with a reduced 5 year overall survival (OS, p = 0.003) and progression-free survival (PFS, p = 0.019). Strikingly, sPD-L1 levels >6.4 pg/ml were indicative of a reduced OS (p = 0.035) and PFS (p = 0.083) in platinum-sensitive patients, while OS and PFS in platinum-resistant patients did not differ when patients were stratified to this cut-off. Conclusions: Our study highlights sPD-L1 and sPD-L2 as complementary biomarkers reflecting clinical status, treatment response and disease outcome of EOC patients. Especially, sPD-L1 may facilitate the identification of high-risk patients with unfavorable disease outcomes despite platinum-sensitivity arguing for additional therapeutic approaches. As sPD-L1 and sPD-L2 are easily accessible via liquid biopsy, the inclusion of sPD-L1 and sPD-L2 in addition to CTC investigation as markers for risk assessment during patient therapy planning and follow-up appears to be a valuable approach.
| S-EPMC6803523 | biostudies-literature
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.
| S-EPMC9354578 | biostudies-literature
Project description:PurposeThe soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC).Materials and methodsWe prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics.ResultsThe median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman's rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline.ConclusionsPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.
| S-EPMC7812012 | biostudies-literature
Project description:Immune checkpoint signaling plays an important role in immunosuppression in multiple myeloma (MM). Blood levels of soluble programmed death-ligand 1 (sPD-L1), a checkpoint-relevant protein, might predict treatment response and survival outcomes in MM patients. We used an enzyme-linked immunosorbent assay to measure serum sPD-L1 levels in 81 newly diagnosed MM patients. We found that myeloma patients had higher sPD-L1 concentrations than healthy controls. The best sPD-L1 cutoff value for predicting disease progression risk was 2.783 ng/mL. The overall response rate to treatment was higher in low sPD-L1 patients than in high sPD-L1 patients. The 3-year progression free survival (PFS) and overall survival (OS) rates for all patients were 16% and 64%, respectively. Multivariate survival analysis including Eastern Cooperative Oncology Group performance status score, treatment response, and sPD-L1 level showed that a less than partial treatment response (PR) and higher sPD-L1 levels (>2.783 ng/ml) were independent prognostic factors for shorter PFS; neither factor was predictive of OS. The serum sPD-L1 level is a valuable biomarker for predicting treatment response and an independent prognostic factor for PFS. PD-1/ PD-L1 blockade may be a promising novel immune-based therapeutic strategy in MM.
| S-EPMC4747402 | biostudies-literature
Project description:Primary outcome(s): Correlation between PD-L1 expression in immune cells and soluble PD-L1 value. Correlation between PD-L1 expression in immune cells or soluble PD-L1 value and PD-L1 expression in tumor tissue. Characterstics of PD-L1 expression in immune cells or soluble PD-L1 value in each gastrointestinal cancer type.
| 2638777 | ecrin-mdr-crc