Soluble programmed cell death protein 1 (sPD‐1) and the soluble programmed cell death ligands 1 and 2 (sPD‐L1 and sPD‐L2) in lymphoid malignancies

Mortensen, Julie Bondgaard; Monrad, Ida; Enemark, Marie Beck; Ludvigsen, Maja; Kamper, Peter; Bjerre, Mette; d’Amore, Francesco

doi:10.1111/ejh.13621

Cited by 8 publications

(9 citation statements)

References 46 publications

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“…In contrast, another work elaborated decreased levels of sPD-L2 in patients with epithelial ovarian cancer [19]. Importantly, the aforementioned investigations report values of sPD-L2 comparable to the numbers described here (1.86-18.25 ng/ml), corroborating validity of our data [17][18][19].…”

Section: Discussionsupporting

confidence: 92%

“…In a population of patients with non-small cell lung cancer treated by nivolumab, sPD-L2 failed to predict response rate, PFS or OS, but was associated with grade 3 and 4 immune related adverse events [ 17 ]. In a larger analysis of lymphoma patients encompassing different entities, sPD-L2 was elevated and revealed distinctive levels between different types of diffuse large B-cell lymphoma [ 18 ]. In contrast, another work elaborated decreased levels of sPD-L2 in patients with epithelial ovarian cancer [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

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Characterization and dynamics of the soluble immunological microenvironment in melanoma patients undergoing radiotherapy

et al. 2022

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Background and purpose Malignant melanoma constitutes an aggressive tumor of the skin, the pathogenesis of which is influenced by immunological processes. In this context, the influence of radiotherapy (RT) on inflammatory markers has not been studied in detail, yet. Materials and methods In this prospective analysis, 28 patients were recruited, 24 of these could be included for further analysis. According to protocol, patients underwent three blood-draws: before, after half of RT-fractions and after completion of RT. Serum levels of programmed death-ligand (PD-L) 1 and 2, interleukin 6 and cytotoxic t-lymphocyte-associated protein 4 were assessed via enzyme-linked immunosorbent assay and compared to healthy volunteers. Correlation with clinical data was attempted. Results Comparing patients with healthy volunteers, a significant difference in the mean baseline serum-level of PD-L1 (90.1 pg/ml vs. 76.7 pg/ml for patients vs. control, respectively; p = 0.024) and PD-L2 (4.4 ng/ml vs. 8.7 ng/ml; p = 0.04) could be found. Increased levels of PD-L1 were only found in patients with prior immunotherapy. There was a tendency for higher interleukin 6 levels in the patients (8.5 pg/ml vs. 0.6 pg/ml; p = 0.052). No significant differences in serum levels could be found between the three time points. Conclusion The present study reveals a characteristic immunological pattern for melanoma patients in comparison to healthy controls. Future studies will have to focus on a putative correlation between immunological markers and clinical outcome parameters.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Characterization and dynamics of the soluble immunological microenvironment in melanoma patients undergoing radiotherapy

et al. 2022

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“…Measurements of sPD-L1 could be useful to predict metastasis and prognosis in soft tissue sarcoma and hepatocellular carcinoma [ 55 , 69 ]. An elevated serum level of sPD-L1 may also represent adverse prognostic factor in certain subtypes of T-cell lymphomas and leukemias [ 113 , 114 ], but there is no general rule for all cancers. sPD-L1 levels vary enormously according to the lymphoma type.…”

Section: Significance Of Soluble Pd-l1 In Cancermentioning

confidence: 99%

“…sPD-L1 levels vary enormously according to the lymphoma type. sPD-L1 levels are higher in patients with diffuse large B-cell lymphoma compared to healthy individuals but lower in patients with follicular lymphoma [ 114 ]. In most of these studies, sPD-L1 is detected by ELISA, but the exact nature of the soluble protein (long form or truncated variants) is not determined.…”

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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“…In recent years, blood-soluble immune checkpoint molecules (such as sPD-1, sPD-L1/2, and sCTLA4) have become measurable. Their relationships with not only lung cancer but also breast cancer, pancreatic cancer, rectal cancer 9 ) , lymphoma 10 ) , and various other malignant diseases have been reported in Japan and other countries. They are detected not only in patients with cancer but also in healthy people 6 , 11 , 12 , 13 ) and patients with diseases other than cancer, such as rheumatoid arthritis, autoimmune hepatitis, and pulmonary fibrosis 5 ) .…”

Section: Discussionmentioning

confidence: 91%

Study of the clinicopathological features of soluble PD-L1 in lung cancer patients

et al. 2023

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Objective: In recent years, an association between serum soluble immune checkpoint molecules (sICMs) and malignant tumors has been reported, which may become important biomarkers in the future. Although several reports have suggested a correlation between sICMs and prognosis, their origin is unclear. In this study, changes in serum soluble PD-L1 (sPD-L1) during the perioperative period and its origin were analyzed in patients with lung cancer. Patients and Methods: Patients with lung tumors (n=39) were included. Samples for sPD-L1 measurements were collected at five time points before and after surgery, and their changes over time were analyzed. ELISA was used to measure sPD-L1 levels. Results: Thirty-nine patients with lung tumors (31, males; 8, females; age, 74 (years) ± 7.7 (range: 51-89) years; malignancy/ benign, 33/6) were enrolled. Eight cases of driver gene mutation-positive tumors were included. Twenty-eight (72%) patients were smokers, and their performance status was 0-1 in all 39 patients. PD-L1 TPS was ≥50%/1-49%/<1% in 8/10/14 patients. Stage I/ II/III/IV/postoperative recurrence of lung cancer was observed in 21/0/6/5/1 patients, respectively. There were no significant correlations between sPD-L1 levels and clinicopathological features and no correlation with PD-L1 TPS. Comparing localized lesions (stages I-III) with advanced lesions (stage IV and postoperative recurrence), the distribution of sPD-L1 was slightly higher in advanced lesions, although the difference was not significant. No obvious changes in sPD-L1 expression were observed before and after surgery. Conclusion: sPD-L1 levels tended to be high in stage III and above lung cancer. There was no change in sPD-L1 levels before and after surgery. sPD-L1 levels did not correlate with the PD-L1 TPS.

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Soluble programmed cell death protein 1 (sPD‐1) and the soluble programmed cell death ligands 1 and 2 (sPD‐L1 and sPD‐L2) in lymphoid malignancies

Cited by 8 publications

References 46 publications

Characterization and dynamics of the soluble immunological microenvironment in melanoma patients undergoing radiotherapy

Characterization and dynamics of the soluble immunological microenvironment in melanoma patients undergoing radiotherapy

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

Study of the clinicopathological features of soluble PD-L1 in lung cancer patients

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