The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes

Ding, Xiang; Wang, Liangliang; Zhu, Yufang; Li, Yandong; Nie, S.; Yang, Jia; Liang, Hua; Weichselbaum, Ralph R.; J, Yu; Hu, Man

doi:10.3389/fimmu.2020.580335

Cited by 10 publications

(4 citation statements)

References 35 publications

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“…Similarly, high baseline sPD-L1 levels were associated with poorer ECOG status and shorter OS in patients treated with chemotherapy and immune checkpoint inhibitors (ICIs) ( 89 ). Higher baseline sPD-L1 levels in patients with glioma treated with radiotherapy were associated with poorer PFS and OS ( 90 ), and high sPD-L1 was considered a biomarker of poor prognosis in HCC patients undergoing curative treatment ( 91 ). High sPD-L1 concentrations were also found to predict future metastases in patients with soft tissue sarcoma ( 92 ), and high pretreatment sPD-L1 was associated with an increased likelihood of disease progression in patients with malignant melanoma ( 65 ).…”

Section: Clinical Importance Of Spd-1 and Spd-l1 In Cancermentioning

confidence: 99%

Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer

Niu

Liu

et al. 2022

Front. Immunol.

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The immune checkpoint pathway consisting of the cell membrane-bound molecule programmed death protein 1 (PD-1) and its ligand PD-L1 has been found to mediate negative regulatory signals that effectively inhibit T-cell proliferation and function and impair antitumor immune responses. Considerable evidence suggests that the PD-1/PD-L1 pathway is responsible for tumor immune tolerance and immune escape. Blockage of this pathway has been found to reverse T lymphocyte depletion and restore antitumor immunity. Antagonists targeting this pathway have shown significant clinical activity in specific cancer types. Although originally identified as membrane-type molecules, several other forms of PD-1/PD-L1 have been detected in the blood of cancer patients, including soluble PD-1/PD-L1 (sPD-1/sPD-L1) and exosomal PD-L1 (exoPD-L1), increasing the composition and functional complications of the PD-1/PD-L1 signaling pathway. For example, sPD-1 has been shown to block the PD-1/PD-L immunosuppressive pathway by binding to PD-L1 and PD-L2, whereas the role of sPD-L1 and its mechanism of action in cancer remain unclear. In addition, many studies have investigated the roles of exoPD-L1 in immunosuppression, as a biomarker for tumor progression and as a predictive biomarker for response to immunotherapy. This review describes the molecular mechanisms underlying the generation of sPD-1/sPD-L1 and exoPD-L1, along with their biological activities and methods of detection. In addition, this review discusses the clinical importance of sPD-1/sPD-L1 and exoPD-L1 in cancer, including their predictive and prognostic roles and the effects of treatments that target these molecules.

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Section: Clinical Importance Of Spd-1 and Spd-l1 In Cancermentioning

confidence: 99%

Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer

Niu

Liu

et al. 2022

Front. Immunol.

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“…In some cases, the level of sPD-L1 is higher for metastatic patients compared to non-metastatic patients, as observed in clear cell renal cell carcinoma [ 45 ], but again there is no general rule. The circulating levels of sPD-L1 represent a predictive biomarker of clinical response to anti-PD-L1 in mesothelioma patients [ 59 ], and it might be a useful marker to predict the outcome in glioma patients receiving radiotherapy [ 112 ]. Measurements of sPD-L1 could be useful to predict metastasis and prognosis in soft tissue sarcoma and hepatocellular carcinoma [ 55 , 69 ].…”

Section: Significance Of Soluble Pd-l1 In Cancermentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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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.

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“…Moreover, there was a positive correlation between sPD-L1 and sVEGFR1 levels in the serum of GBM patients. Higher sPD-L1 levels are associated with worse prognosis of GBM patients [ 20 ]. In patients with renal cell carcinoma, higher serum sPD-L1 levels suggest poor reactivity to sunitinib [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages

Liu

Sun

et al. 2023

BMC Cancer

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Purpose The combined application of immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapy has shown synergistic effects on glioblastoma (GBM). As important resources of PD-L1 in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have significant impact of the efficiency of ICIs. However, the effects of anti-angiogenesis agents on immune checkpoints expression are not fully understood. Method GBM-educated macrophages were generated from circulating monocytes of healthy controls and GBM patients under the education of GBM cell line. Surface expression of PD-L1 and VEGFR1 on GBM-educated macrophages was analyzed. VEGFR1 NAb and soluble VEGFR1 (sVEGFR1) were added and their effects on PD-L1 expression on TAMs was investigated. Serum soluble PD-L1 (sPD-L1) and sVEGFR1 levels in GBM patients were measured and their correlation was analyzed. Result The expression intensity of PD-L1 on GBM-educated macrophages was higher and its up-regulation partially depends on VEGFR1 signaling pathway. GBM-educated macrophages secreted less levels of soluble VEGFR1 (sVEGFR1), and exogenous sVEGFR1 down-regulated PD-L1 expression intensity. PD-L1 blockade promoted the secretion of sVEGFR1. Finally, sVEGFR1 and sPD-L1 in serum of GBM patients were overexpressed, and a positive correlation was found. Conclusion These findings reveal the interaction between PD-L1 and VEGFR1 signaling pathway in GBM-educated macrophages. VEGFR1 is involved with PD-L1 overexpression, which can be impeded by autocrine regulation of sVEGFR1. sVEGFR1 secretion by GBM-educated macrophages can be promoted by PD-L1 blockade. Taken together, these findings provide evidences for the combined application of ICIs and anti-angiogenesis therapies in the treatment of GBM.

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The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes

Cited by 10 publications

References 35 publications

Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer

Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages

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