Soluble Ligand of the Immune Checkpoint Receptor (sPD-L1) in Blood Serum of Patients with Renal Cell Carcinoma

Kushlinskii, N. E.; Es, Gershteĭn; Morozov, Alexei; Goryacheva, I O; Филипенко, М. Л.; Alferov, A.A.; Bezhanova, Svetlana; Базаев, В В; Казанцева, И. А.

doi:10.1007/s10517-019-04349-8

Cited by 19 publications

(12 citation statements)

References 15 publications

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“…32 Other studies have demonstrated that a higher serum sPD-L1 level was observed in HCC and renal cell carcinoma patients with a larger tumor size and metastasis. 16,33 These findings suggest that the serum sPD-L1 level varies depending on the tumor burden. All the patients enrolled in the present study had recurrent disease after definitive local treatment or advanced NSCLC, and some patients had already been treated with some type of systemic therapy; therefore, the relationship between the primary tumor size or the clinical stage and the sPD-L1 level could not be evaluated.…”

Section: Discussionmentioning

confidence: 87%

Association between serum level soluble programmed cell death ligand 1 and prognosis in patients with non‐small cell lung cancer treated with anti‐PD‐1 antibody

Murakami¹,

Shibaki²,

Yoshida³

et al. 2020

Thoracic Cancer

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Background: Programmed cell death ligand 1 (PD-L1) is known to have soluble forms aside from its membrane-bound forms. The aim of this study was to evaluate the predictive and prognostic values of serum soluble PD-L1 (sPD-L1) in patients with non-small cell lung cancer (NSCLC) who were treated with anti-PD-1 antibody. Methods: A total of 233 patients were enrolled in this study. We assessed the level of serum sPD-L1 before anti-PD-1 antibody treatment (pembrolizumab or nivolumab) and evaluated the correlation with PD-L1 expression on tumor cells, the response to anti-PD-1 antibody treatment, and patient outcome. Results: The median serum sPD-L1 concentration was 67.7 (range, 25 to 223) pg/mL. A weak correlation between serum sPD-L1 and tumor PD-L1 expression was observed. The disease control rate in the high sPD-L1 group (≥90 pg/mL) was significantly lower than that in the low sPD-L1 group (<90 pg/mL) (37% vs. 57%, P = 0.0158). The progression-free survival (PFS) and overall survival (OS) in the high sPD-L1 group were significantly shorter than those in the low sPD-L1 group (median PFS, 57 days vs. 177 days, P = 0.011; median OS, 182 days vs. not reached, P < 0.001). The high level of serum sPD-L1 was independently associated with a shorter PFS (hazard ratio [HR], 1.910; P = 0.061) and OS (HR, 2.073; P = 0.034) in multivariate analysis. Conclusions: The serum sPD-L1 level, which was only weakly correlated with the tumor PD-L1 expression level, was an independent predictive and prognostic biomarker for NSCLC patients receiving anti-PD-1 antibody. Key pointsSignificant findings of the study: The disease control rate in the high sPD-L1 group was significantly lower than that in the low sPD-L1 group. The progression-free survival (PFS) and overall survival (OS) in the high sPD-L1 group were significantly shorter than those in the low sPD-L1 group. The high level of serum sPD-L1 was independently associated with a shorter PFS and OS in multivariate analysis. What this study adds: This study demonstrated that serum sPD-L1 level was an independent predictive and prognostic biomarker for NSCLC patients receiving anti-PD-1 antibody. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Discussionmentioning

confidence: 87%

Association between serum level soluble programmed cell death ligand 1 and prognosis in patients with non‐small cell lung cancer treated with anti‐PD‐1 antibody

Murakami¹,

Shibaki²,

Yoshida³

et al. 2020

Thoracic Cancer

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“…Similar to membrane-binding PD-L1, soluble PD-L1 (sPD-L1) is currently thought to contribute to systemic immunosuppression (18,19). Recently, a few published reports have shown that sPD-L1 is an indispensable predictor in various types of cancer (20)(21)(22), especially for checkpoint blockade treatments (23,24). In addition, some studies have referred to circulating sPD-L1 as a surrogate marker for tumor PD-L1 expression (25).…”

Section: Introductionmentioning

confidence: 99%

The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas

et al. 2020

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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.

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“…In these patients, sPD-L1 and sPD-1 are correlated with a poor prognosis, 24 tumor size and tumor grade. 25,26 The impact of sPD-L1 and sPD-1 on the response to treatment and survival in mccRCC patients is still unknown. The aim of this study was to determine the prognostic/predictive value of sPD-L1 and sPD-1 in mccRCC patients treated with the antiangiogenic agents sunitinib or bevacizumab.…”

Section: Introductionmentioning

confidence: 99%

Soluble forms of PD-L1 and PD-1 as prognostic and predictive markers of sunitinib efficacy in patients with metastatic clear cell renal cell carcinoma

et al. 2020

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Metastatic clear cell renal cell carcinoma (mccRCC) benefits from several treatment options in the first-line setting with VEGFR inhibitors and/or immunotherapy including anti-PD-L1 or anti-PD1 agents. Identification of predictive biomarkers is highly needed to optimize patient care. Circulating markers could reflect the biology of metastatic disease. Therefore, we evaluated soluble forms of PD-L1 (sPD-L1) and PD-1 (sPD-1) in mccRCC patients. The levels of sPD-L1 and sPD-1 were evaluated from plasma samples of mccRCC patients before they received a first-line treatment (T0) by the VEGFR inhibitor sunitinib (50 patients) or by the anti-VEGF bevacizumab (37 patients). The levels of sPD-L1 and sPD-1 were correlated to clinical parameters and progression-free survival (PFS). High levels of sPD-1 or sPDL1 were not correlated to PFS under bevacizumab while they were independent prognostic factors of PFS in the sunitinib group. Patients with high T0 plasmatic levels of sPD-L1 had a shorter PFS (11.3 vs 22.5 months, p = .011) in the sunitinib group. Equivalent shorter PFS was found with high levels of sPD-1 (8.6 vs 14.1 months, p = .009). mccRCC patients with high plasmatic levels of sPD-L1 or sPD-1 are poor responders to sunitinib. sPD-L1 or sPD-1 could be a valuable tool to guide the optimal treatment strategy including VEGFR inhibitor.

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Soluble Ligand of the Immune Checkpoint Receptor (sPD-L1) in Blood Serum of Patients with Renal Cell Carcinoma

Cited by 19 publications

References 15 publications

Association between serum level soluble programmed cell death ligand 1 and prognosis in patients with non‐small cell lung cancer treated with anti‐PD‐1 antibody

Association between serum level soluble programmed cell death ligand 1 and prognosis in patients with non‐small cell lung cancer treated with anti‐PD‐1 antibody

The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas

Soluble forms of PD-L1 and PD-1 as prognostic and predictive markers of sunitinib efficacy in patients with metastatic clear cell renal cell carcinoma

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