The clinical implication of soluble PD-L1 (sPD-L1) in patients with breast cancer and its biological function in regulating the function of T lymphocyte

Han, Bing; Dong, Lei; Zhou, Jing; Yang, Yan; Guo, Jiaxun; Xuan, Qijia; Gao, Kun; Xu, Zhenguo; Lei, Wenhua; Wang, Jingxuan; Zhang, Qingyuan

doi:10.1007/s00262-021-02898-4

Cited by 37 publications

(37 citation statements)

References 53 publications

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“…In this study, native human sPD-L1 was found to induce suppressive effects on activated T-cells, thus mimicking the effect of mPD-L1 [ 128 ]. A recent study using sPD-L1 isolated from the plasma of patients with recurrent/metastatic breast cancer demonstrated that sPD-L1 can inhibit T lymphocyte function, acting as a negative regulatory element in cellular immunity [ 129 ]. Similar observations have been reported previously in experimental (in vitro) studies using sPD-L1 released from lung cancer cells [ 130 ].…”

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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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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“…141 PD-L1 can also be found as in patients' plasma. A recent study by Han et al, 142 on 208 patients with recurrent/ metastatic BC before receiving first-line therapy, showed that high soluble PD-L1 level (8.774 ng/ml) and visceral metastasis were independent factors associated with poor prognosis. Both exosomal and soluble PD-L1 seem to properly reflect the level of the patient immunosuppressive state.…”

Section: Biomarkers With Demonstrated Predictive Valuementioning

confidence: 99%

Refining patient selection for breast cancer immunotherapy: beyond PD-L1

Radosevic‐Robin¹,

Penault‐Llorca²

2021

ESMO Open

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Therapies that modulate immune response to cancer, such as immune checkpoint inhibitors, began an intense development a few years ago; however, in breast cancer (BC), the results have been relatively disappointing so far. Finding biomarkers for better selection of BC patients for various immunotherapies remains a significant unmet medical need. At present, only tumour tissue programmed death-ligand 1 (PD-L1) and mismatch repair deficiency status are approved as theranostic biomarkers for programmed cell death-1 (PD-1)/PD-L1 inhibitors in BC. However, due to the complexity of tumour microenvironment (TME) and cancer response to immunomodulators, none of them is a perfect selector. Therefore, an intense quest is ongoing for complementary tumour-or host-related predictive biomarkers in breast immuno-oncology. Among the upcoming biomarkers, quantity, immunophenotype and spatial distribution of tumour-infiltrating lymphocytes and other TME cells as well as immune gene signatures emerge as most promising and are being increasingly tested in clinical trials. Biomarkers or strategies allowing dynamic assessment of BC response to immunotherapy, such as circulating/exosomal PD-L1, quantity of white/ immune blood cell subpopulations and molecular imaging are particularly suitable for immunotreatment monitoring. Finally, host-related factors, such as microbiome and lifestyle, should also be taken into account when planning integration of immunomodulating therapies into BC management. As none of the biomarkers taken separately is accurate enough, the solution could come from composite biomarkers, which would combine clinical, molecular and immunological features of the disease, possibly powered by artificial intelligence.

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“…For plasma samples, lithium heparin BD blood collection vials were used and promptly centrifuged within 4 h to obtain fresh plasma. The plasma specimens were stored at −80 • C until testing [47]. In general, the processing time and storage conditions of blood samples are critical for the stable and reliable measurement of target analytes [61].…”

Section: Blood Samplementioning

confidence: 99%

“…Soluble PD-L1, which can attach to PD-1, is usually generated following proteolytic cleavage of membrane-bound PD-L1 by translation of alternatively spliced mRNA or matrix metalloproteinase [76]. Soluble PD-L1 has been reported to be a potential prognostic predictor in several cancers [47]. Soluble PD-L1 indicates an anti-immune response and cooperatively affects tumor progression.…”

Section: Soluble Pd-l1mentioning

confidence: 99%

“…Regarding immunotherapy, therapeutic anti-PD-L1 might be absorbed by soluble PD-L1 before reaching TC, which alters the killing effect of BC cells on IC [60]. Meanwhile, a specific anti-PD-L1 antibody agent might suppress the expression of soluble PD-L1 and remove its blocking effect on the PD-1 negative signaling pathway, leading to improving T cell viability and enhancing the killing of BC cells [47]. There have been several studies investigating soluble PD-L1 because abnormalities in this factor are involved in early and long-term immune modulation.…”

Section: Soluble Pd-l1mentioning

confidence: 99%

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Currently Used Laboratory Methodologies for Assays Detecting PD-1, PD-L1, PD-L2 and Soluble PD-L1 in Patients with Metastatic Breast Cancer

Jeong

Lee

Park

et al. 2021

Cancers

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Approximately 20% of breast cancer (BC) patients suffer from distant metastasis. The incidence and prevalence rates of metastatic BC have increased annually. Immune checkpoint inhibitors are an emerging area of treatment, especially for metastatic patients with poor outcomes. Several antibody drugs have been developed and approved for companion testing of the programmed death protine-1 (PD-1) axis. We reviewed currently used laboratory methodologies for assays determining PD-1 axis to provide a comprehensive understanding of principles, advantages, and drawbacks involved in their implementation. The most commonly used method is immunohistochemistry (92.9%) for PD-L1 expression using tissue samples (96.4%). The commonly used anti-PD-L1 antibody clone were commercially available 22C3 (30.8%), SP142 (19.2%), SP263 (15.4%), and E1L3N (11.5%). Enzyme-linked immunosorbent assay and electrochemiluminescent immunoassay that target soluble PD-ligand (L)1 were developed and popularized in 2019–2021, in contrast to 2016–2018. Easy accessibility and non-invasiveness due to the use of blood samples, quantitative outputs, and relatively rapid turnaround times make them more preferable. Regarding scoring methods, a combination of tumor and immune cells (45.5% in 2016–2018 to 57.1% in 2019–2021) rather than each cell alone became more popular. Information about antibody clones, platforms, scoring methods, and related companion drugs is recommended for reporting PD-L1 expression.

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The clinical implication of soluble PD-L1 (sPD-L1) in patients with breast cancer and its biological function in regulating the function of T lymphocyte

Cited by 37 publications

References 53 publications

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

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

Refining patient selection for breast cancer immunotherapy: beyond PD-L1

Currently Used Laboratory Methodologies for Assays Detecting PD-1, PD-L1, PD-L2 and Soluble PD-L1 in Patients with Metastatic Breast Cancer

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