Role of ADAM10 as a CD30 Sheddase in Classical Hodgkin Lymphoma

Hansen, Hinrich P.; Leme, Adriana Franco Paes; Hallek, Michael

doi:10.3389/fimmu.2020.00398

Cited by 11 publications

(11 citation statements)

References 31 publications

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“…Both ADAM10 and ADAM17 can cleave PD-L1 from the surface of vesicles and cells [ 97 ]. ADAM10 has been shown to release different proteins, such as the transmembrane receptor CD30 implicated in Hodgkin Lymphoma, releasing it either as a molecule embedded in the membrane of extracellular vesicles or as a cleaved soluble ectodomain [ 98 ]. The protease does the same thing with PD-L1 and there are probably other “sheddases” contributing to the release of sPD-L1 from cells.…”

Section: Generation Of Soluble Pd-l1: Proteolysis and Alternative Splicingmentioning

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: Generation Of Soluble Pd-l1: Proteolysis and Alternative Splicingmentioning

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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“…However, BB-3644 inhibits additional MMPs and contributed to dose-limiting musculoskeletal toxicities in human trials [ 81 ]. More selective ADAM10 inhibitors are in development, with promising improvements in off-target toxicities [ 82 ].…”

Section: Target Antigens For Approved Adcs and Their Endocytosis Characteristicsmentioning

confidence: 99%

Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)—A Necessity for Future ADC Research and Development

2021

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Biologically-based therapies increasingly rely on the endocytic cycle of internalization and exocytosis of target receptors for cancer therapies. However, receptor trafficking pathways (endosomal sorting (recycling, lysosome localization) and lateral membrane movement) are often dysfunctional in cancer. Antibody-drug conjugates (ADCs) have revitalized the concept of targeted chemotherapy by coupling inhibitory antibodies to cytotoxic payloads. Significant advances in ADC technology and format, and target biology have hastened the FDA approval of nine ADCs (four since 2019). Although the links between aberrant endocytic machinery and cancer are emerging, the impact of dysregulated internalization processes of ADC targets and response rates or resistance have not been well studied. This is despite the reliance on ADC uptake and trafficking to lysosomes for linker cleavage and payload release. In this review, we describe what is known about all the target antigens for the currently approved ADCs. Specifically, internalization efficiency and relevant intracellular sorting activities are described for each receptor under normal processes, and when complexed to an ADC. In addition, we discuss aberrant endocytic processes that have been directly linked to preclinical ADC resistance mechanisms. The implications of endocytosis in regard to therapeutic effectiveness in the clinic are also described. Unexpectedly, information on endocytosis is scarce (absent for two receptors). Moreover, much of what is known about endocytosis is not in the context of receptor-ADC/antibody complexes. This review provides a deeper understanding of the pertinent principles of receptor endocytosis for the currently approved ADCs.

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“…In the case of the neoplastic process or cancer, it has been shown that platelets, as a result of the interaction, mediated by TLR-4 receptors, with neoplastic cells, secrete substances from α granules, such as HMGB1 (high mobility group box 1) protein and TNF-β, which leads to the activation of the immune system and enhancement of inflammation, but also to an increase in the invasiveness of cancer cells ( 76 ). The condition of increased potential for cancer metastasis has also been found when increased platelet aggregation has been registered, as this condition, caused by the activity of, among others, a member of the metalloproteinases family (MMP - matrix metalloproteinases) - ADAM-10 (a disintegrin and metalloproteinase) and the NLRP3 inflammasome, increases inflammation ( 12 , 14 , 76 , 103 , 104 ). It has also been reported that cancer cells, by secreting thrombin, transform fibrinogen into fibrin ( 12 , 60 , 105 ).…”

Section: Platelets and Inflammationmentioning

confidence: 99%

What Function Do Platelets Play in Inflammation and Bacterial and Viral Infections?

et al. 2021

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The article presents the function of platelets in inflammation as well as in bacterial and viral infections, which are the result of their reaction with the endovascular environment, including cells of damaged vascular endothelium and cells of the immune system. This role of platelets is conditioned by biologically active substances present in their granules and in their specific structures – EV (extracellular vesicles).

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Role of ADAM10 as a CD30 Sheddase in Classical Hodgkin Lymphoma

Cited by 11 publications

References 31 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

Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)—A Necessity for Future ADC Research and Development

What Function Do Platelets Play in Inflammation and Bacterial and Viral Infections?

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