Plasma levels of soluble programmed death ligand-1 may be associated with overall survival in nonsmall cell lung cancer patients receiving thoracic radiotherapy

Zhao, Jing; Zhang, Peng; Wang, Jianhua; Xi, Qingsong; Zhao, Xueqi; Ji, Minjun; Hu, Guohong

doi:10.1097/md.0000000000006102

Cited by 31 publications

(31 citation statements)

References 45 publications

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“…Another report studied the variation of sPD-L1 in patients with locally advanced or inoperable NSCLC undergoing radiotherapy. 22 This study showed that sPD-L1 levels measured after 2 and 4 weeks of radiotherapy significantly decreased compared to pre-radiotherapy levels and that patients with lower baseline sPD-L1 levels had longer OS than those with higher sPD-L1 levels.…”

Section: Discussionmentioning

confidence: 56%

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Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

et al. 2018

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Immune checkpoint inhibitors, as nivolumab, are used in advanced non-small cell lung cancer (NSCLC). However, no associated biomarker is validated in clinical practice with this drug. We investigated herein immune-related blood markers in patients with advanced NSCLC treated with nivolumab. Plasma of 43 consecutive patients were prospectively collected at time of the diagnosis of cancer, at the initiation of nivolumab and at the first tumour evaluation (2 months). Concentrations of PD-L1 (sPD-L1), soluble PD-L2 (sPD-L2), Interleukine-2 (sIl-2), Interferon-gamma (sIFN-γ), and Granzyme B (sGranB) were quantified by ELISA. Cell free RNA was quantified by Reverse Transcriptase -PCR), and plasmatic microRNAs (miRNAs) were evaluated by targeted sequencing. Expression of PD-L1 on tumour biopsies was performed by immunohistochemistry using E13LN. High sPD-L1 at 2 months and increase of sPD-L1 concentrations were associated with poor response and absence of clinical benefit (nivolumab treatment less than 6 months). The variation of sPD-L1 concentrations were confirmed by RNA quantification. sPD-L1 concentrations were not correlated with PD-L1 expression on corresponding tumour samples. Low sGranB at nivolumab initiation was also associated with poor response. High sPD-L1 and low sGranB were associated with poor progression-free survival (PFS) and overall survival (OS). Low sPD-L2, low sIl-2 and high sIFN-γ were associated with grade 3-4 toxicities. Finally, miRNA screening showed that patients with clinical benefit (n = 9) had down-expression of miRNA-320b and -375 compared to patients with early progression at 2 months (n = 9). In conclusion, our results highlight the interest of circulating biomarkers in patients treated with nivolumab.

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Section: Discussionmentioning

confidence: 56%

“…The presence of soluble PD-L1 (sPD-L1) has already been established in patients with NSCLC with a prognostic impact of sPD-L1 concentrations. [20][21][22] Its prognostic and predictive impact with ICIs is however still unknown.…”

Section: Introductionmentioning

confidence: 99%

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

et al. 2018

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“…The characteristics of the included studies are listed in Table 1 . [ 18 – 21 , 23 , 24 , 27 ] The publication time varied from 2014 to 2017. Studies were from Germany, Japan, Korea, and China with different kinds of solid tumors, including lung cancer, gastric cancer, biliary tract cancer, hepatocellular carcinoma, and renal cell carcinoma.…”

Section: Resultsmentioning

confidence: 99%

Prognostic significance of circulating soluble programmed death ligand-1 in patients with solid tumors

Wei

Wang

et al. 2018

Medicine

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Background:The prognostic significance of circulating soluble programmed death ligand-1 (sPD-L1) in patients with solid tumors remains unclear. We performed a meta-analysis to address this issue.Methods:Several electronic databases were searched from January 1970 to May 2017. The hazard ratios (HRs) and 95% confidence interval (95% CI) were calculated to determine the relationship between the level of soluble PD-L1 in peripheral blood and patient overall survival.Results:A total of 1040 patients with solid tumors from 8 eligible studies were included in the present meta-analysis. The pooled HR suggested that a high level of soluble PD-L1 (sPD-L1) in peripheral blood was significantly correlated with a worse overall survival (HR = 2.26, 95% 1.83–2.80, Z = 7.51, P < .001).Conclusion:The present meta-analysis demonstrated that a high level of soluble PD-L1 in peripheral blood significantly predicts poor prognosis in patients with solid tumors, suggesting that high level of sPD-L1 may serve as a predictive biomarker for poor prognosis.

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“…sPD-L1 was correlated with prognosis as well as response to immune checkpoint inhibitors in extracranial tumours and might be a promising marker to measure systemic immune suppression. [14][15][16][17][18][19][20][21][22] Using a sandwich ELISA, we detected sPD-L1 in the plasma of patients with brain tumour and the highest concentration was evident in patients with glioma. No correlation of sPD-L1 and tissue PD-L1 expression was observed.…”

Section: Discussionmentioning

confidence: 99%

Soluble PD-L1 is associated with local and systemic inflammation markers in primary and secondary brain tumours

et al. 2020

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BackgroundImmune-modulatory treatments have so far shown limited clinical activity in primary brain tumours. We aimed to investigate soluble programmed death receptor ligand 1 (sPD-L1) as systemic inflammation parameter in patients with brain tumour.MethodsEDTA plasma was collected from 81 glioma (55 glioblastoma (GBM), 26 lower-grade glioma (LGG)), 17 meningioma and 44 brain metastasis (BM) patients and 24 controls. sPD-L1 concentrations were determined by ELISA. Correlations with the local tumour microenvironment were assessed by immunohistochemical analysis for PD-L1, CD3 and CD8.ResultssPD-L1 was detected in 62 out of 166 (37.7%) patients (glioma: 41/81, 50.6%; meningioma: 5/17, 29.4%; BM: 7/44, 15.9%; controls: 9/24, 37.5%; p=0.002). sPD-L1 concentrations were lower in BM than in LGG (p=0.003) or GBM (p<0.001). Membranous PD-L1 expression on tumour cells was not associated with sPD-L1 concentrations (p=0.953). sPD-L1 concentration was inversely correlated with the density of CD8+ (r=−0.713, p=0.001) and CD3+ (r=−0.484, p=0.042) tumour-infiltrating lymphocytes in LGG. sPD-L1 is correlated with neutrophil counts (r=−0.318, p=0.045) and C reactive protein levels (r=−0.363, p=0.008) in GBM. sPD-L1+ patients had longer overall survival in GBM (p=0.006) and worse OS in LGG (p=0.028).ConclusionssPD-L1 is detectable in a fraction of patients with brain tumour. Although it is not correlated with tissue PD-L1 expression, correlations with other local and systemic inflammation parameters could be detected in LGG and GBM.

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Plasma levels of soluble programmed death ligand-1 may be associated with overall survival in nonsmall cell lung cancer patients receiving thoracic radiotherapy

Abstract: Supplemental Digital Content is available in the text

Cited by 31 publications

References 45 publications

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

Prognostic significance of circulating soluble programmed death ligand-1 in patients with solid tumors

Soluble PD-L1 is associated with local and systemic inflammation markers in primary and secondary brain tumours

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