Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Santoso, Budi; Sa’adi, Ashon; Dwiningsih, Sri Ratna; Tunjungseto, Arif; Widyanugraha, Muhammad Yohanes Ardianta; Mufid, Alfin Firasy; Rahmawati, Nanda Yuli; Ahsan, Fadhil

doi:10.1111/aji.13296

Cited by 26 publications

(34 citation statements)

References 25 publications

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“… [ 143 ] Endometriosis Elevated level of sPD-L1 in the serum and peritoneal fluid of patients with endometriosis vs. control. [ 144 ] Idiopathic pulmonary fibrosis (IPF) Elevated concentrations of sPD-L1 in the serum of IPF patients compared to healthy population. [ 27 ] Immune thrombocytopenia (ITP) Decreased levels of sPD-L1 in patients with newly diagnosed ITP compared to patients with chronic ITP.…”

Section: Soluble Pd-l1 Beyond Cancermentioning

confidence: 99%

“…Elevated levels of sPD-L1 have been measured in the serum and the peritoneal fluid of endometriosis patients compared to controls. The protein could thus represent a biomarker for endometriosis [ 144 ]. In cases of preeclampsia (a pregnancy complication characterized by high blood pressure and damages to organs such as the liver and kidneys), the maternal sPD-L1 level can increase a little but it is essentially sPD-1 levels which are significantly enhanced in preeclamptic women compared to normotensive pregnant women [ 185 ].…”

Section: Soluble Pd-l1 Beyond Cancermentioning

confidence: 99%

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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: Soluble Pd-l1 Beyond Cancermentioning

confidence: 99%

Section: Soluble Pd-l1 Beyond 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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“…In a study on endometriosisassociated infertility, Santoso B et al have investigated the level of soluble(s) CTLA, sPD-1, sPD-L1, and HLA-G in endometriosis. HLA-G may act similar to IC molecules presented on cytotoxic T cells (CD8+T cells), they have found HLA-G accompanied sPD-L1 and sCTLA-4 may implicated in the pathological mechanisms of endometriosis-related infertility (39). Schwich E et al demonstrated that sHLA-G1 significantly increased the frequency of ILT-2 receptors on CD8+ T cells and might be involved with other IC molecules to generate an immunosuppressive or exhausted phenotype (40).…”

Section: Bio-functional Character Of Hla-gmentioning

confidence: 99%

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

2021

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Maternal-fetal immune-tolerance occurs throughout the whole gestational trimester, thus a mother can accept a genetically distinct fetus without immunological aggressive behavior. HLA-G, one of the non-classical HLA class I molecules, is restricted-expression at extravillous trophoblast. It can concordantly interact with various kinds of receptors mounted on maternally immune cells residing in the uterus (e.g. CD4+ T cells, CD8+ T cells, natural killer cells, macrophages, and dendritic cells) for maintaining immune homeostasis of the maternal-fetus interface. HLA-G is widely regarded as the pivotal protective factor for successful pregnancies. In the past 20 years, researches associated with HLA-G have been continually published. Indeed, HLA-G plays a mysterious role in the mechanism of maternal-fetal immune-tolerance. It can also be ectopically expressed on tumor cells, infected sites and other pathologic microenvironments to confer a significant local tolerance. Understanding the characteristics of HLA-G in immunologic tolerance is not only beneficial for pathological pregnancy, but also helpful to the therapy of other immune-related diseases, such as organ transplant rejection, tumor migration, and autoimmune disease. In this review, we describe the biological properties of HLA-G, then summarize our understanding of the mechanisms of fetomaternal immunologic tolerance and the difference from transplant tolerance. Furthermore, we will discuss how HLA-G contributes to the tolerogenic microenvironment during pregnancy. Finally, we hope to find some new aspects of HLA-G in fundamental research or clinical application for the future.

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“…For example, immunotherapy either by targeting T cells or administration of immune checkpoint inhibitors has emerged as a promising treatment for chronic inflammatory diseases such as rheumatoid arthritis (Wei et al, 2020) and difficultto-treat cancers. As our understanding of the role(s) of T cells and other immune cells in the etiology of endometriosis expands, we may soon be able to capitalize on the remarkable progress made by developing and implementing immunotherapy as an endometriosis treatment (Santoso et al, 2020). Our own work that identified the mechanisms responsible for the altered metabolic phenotype of the peritoneal mesothelial cells in women with endometriosis has allowed us to investigate the repurposing of drugs that have impact on lactate production (Horne et al, 2019a).…”

Section: Discussionmentioning

confidence: 99%