NK Cells as Potential Targets for Immunotherapy in Endometriosis

Ścieżyńska, Aneta; Komorowski, Michał; Soszyńska, Marta; Malejczyk, Jacek

doi:10.3390/jcm8091468

Cited by 61 publications

(47 citation statements)

References 153 publications

(226 reference statements)

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“…The presence of soluble molecules in the peritoneal cavity not only highlights their involvement in the underlying disease but also may reflect the cellular sources of the four molecules, which might not be abundant in the gynecological organs, especially in fallopian and uterus. Moreover, it is noteworthy to mention that immune checkpoint blockade is a new paradigm in targeted endometriosis immunotherapy 25 . An alteration of lymphocytic activation and increased estrogen production by immune checkpoint molecules in endometriosis is believed to play a critical role in development of disease severity, limiting the clearance of ectopic endometrial‐like lesion by activated NK cells or cytotoxic T cells 8,19,25 .…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, it is noteworthy to mention that immune checkpoint blockade is a new paradigm in targeted endometriosis immunotherapy 25 . An alteration of lymphocytic activation and increased estrogen production by immune checkpoint molecules in endometriosis is believed to play a critical role in development of disease severity, limiting the clearance of ectopic endometrial‐like lesion by activated NK cells or cytotoxic T cells 8,19,25 . As the elevated expression of either soluble or membrane‐bound checkpoint molecules was clearly observed, further studies need to address whether the use of checkpoint inhibitors could remodel the immune activation leading to abrogation of the establishment or progression of endometriosis lesions.…”

Section: Resultsmentioning

confidence: 99%

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

Santoso

Sa’adi

Dwiningsih

et al. 2020

American J Rep Immunol

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Problem: Soluble immune checkpoint molecules constitute the emerging novel mediators in immune regulation. Their role in the pathogenesis of endometriosis has not been fully addressed. In this study, we aimed to investigate the relationship between the clinical manifestation of endometriosis-associated infertility and the level of four soluble immune checkpoints: sCTLA4, sHLA-G, sPD-1, and sPD-L1. Method of study: The soluble immune checkpoint concentrations in serum and peritoneal fluid from 88 patients who underwent laparoscopy were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. Results: Endometriosis cases were evident to have significantly higher levels of serum sPD-L1 and all four molecules in peritoneal fluid compared to non-endometriosis control. Contrary, no significant differences were found in the concentration of serum sCTLA-4, sHLA-G and, sPD-1 between endometriosis and control group. There were significant positive correlations between serum and peritoneal fluid concentrations of sCTLA-4, sPD-L1, and sHLA-G. Serum sPD-L1 could discriminate endometriosis-related infertility to other pathological control. At a cutoff of 14,61 pg/ mL, serum sPD-L1 had a sensitivity of 77% and specificity of 83%. Moreover, sPD-L1 level showed positive correlations with pelvic adhesion score and myeloid cell count. Conclusion: The elevated level of sPD-L1 in serum and immune checkpoint molecules in the peritoneal fluid could represent the hallmark of immune regulation in endometriosis. Serum sPD-L1 could serve as a potential noninvasive endometriosis biomarker. Also, the immune compartment related to the local immune checkpoint molecules may be implicated in biological mechanisms underlying endometriosisrelated infertility.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Santoso

Sa’adi

Dwiningsih

et al. 2020

American J Rep Immunol

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“…Additionally, the antitumor response was enhanced after the use of a CD200-neutralizing antibody in those patients. Ścieżyńska et al [ 41 ] indicated that NK cells may be an immunotherapy target by blocking its negative control checkpoints in EMS patients.…”

Section: Discussionmentioning

confidence: 99%

CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis

Abramiuk

Grywalska

Korona-Głowniak

et al. 2020

JCM

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The causes of endometriosis (EMS) remain unknown; however, a number of immunological abnormalities contribute to the pathogenesis of the disease. The cluster of differentiation-200 (CD200) and its receptor (CD200R) maintain peripheral self-tolerance by negatively regulating immune responses. In this comparative cross-sectional study, we investigated the expression of CD200 and CD200R on T and B lymphocytes and the serum level of soluble CD200 (sCD200) using flow cytometry and ELISA, respectively. Peripheral blood samples were collected from 54 female patients and 20 healthy, age-matched controls. Results were tested for correlation with disease severity and selected clinical parameters. We demonstrated that the differences in sCD200 levels (p = 0.001), the frequencies of CD200-positive T and B lymphocytes (p < 0.001 and p = 0.004, respectively), and the frequencies of CD200R-positive T and B lymphocytes (p < 0.001 for all comparisons) in the study group correlated positively with disease severity. Receiver operating characteristic (ROC) analysis indicated that aberrant expression of CD200/CD200R might serve as a marker to distinguish between EMS cases. Finally, negative co-stimulatory factors may contribute to the induction and persistence of inflammation associated with EMS. It seems that it is essential to determine whether alteration in the CD200/CD200R pathway can be therapeutically targeted in EMS.

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“…In fact, EM is characterized by a downregulation of NK cell cytotoxicity ( 179 , 180 ), probably due to the consistent amount of inhibitory cytokines in the peritoneal fluid of patients affected by EM, or to an augmented presence of several inhibitory NK cell receptors. It is reasonable to speculate that the incapacity of uNK cells, as well as macrophages, to recognize and eliminate endometriotic cells in the peritoneal cavity, can allow their survival and growth, leading to development and progression of EM ( 181 ).…”

Section: Endometriosis and Immunotherapymentioning

confidence: 99%

Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target

et al. 2021

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Endometriosis (EM) is a chronic disease characterized by the presence and proliferation of functional endometrial glands and stroma outside the uterine cavity. Ovaries and pelvic peritoneum are the most common locations for endometrial ectopic tissue, followed by deep infiltrating EM sites. The cyclic and recurrent bleeding, the progressive fibrosis and the peritoneal adhesions of ectopic endometrial glands, may cause different symptoms depending on the origin involved. EM is a frequent clinical condition affecting around 10% of women of mainly reproductive age, as well as in post-menopausal women and adolescents, especially with uterine anomalies. The risk of developing EM depends on a complex interaction between genetic, immunological, hormonal, and environmental factors. It is largely considered to arise due to a dysfunction of immunological surveillance. In fact, women with EM exhibit altered functions of peritoneal macrophages, lymphocytes and natural killer cells, as well as levels of inflammatory mediators and growth factors in the peritoneal fluid. In EM patients, peritoneal macrophages are preponderant and highly active compared to healthy women. Peritoneal macrophages are able to regulate the events that determine the production of cytokines, prostaglandins, growth factors and complement components. Several studies have shown alteration in the regulation of the complement activation, leading to chronic inflammation characteristic of EM. Aberrant regulation/activation of the complement system has been observed in the peritoneal cavity of women affected by EM. Thus, complement inhibition may represent a new approach for the treatment of EM, given that a number of complement inhibitors are under pre-clinical and clinical development. Such an intervention may provide a broader therapeutic control of complement-mediated inflammatory damage in EM patients. This review will focus on our current understanding of the role of complement activation in EM and possible modalities available for complement-based therapy.

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NK Cells as Potential Targets for Immunotherapy in Endometriosis

Cited by 61 publications

References 153 publications

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

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

CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis

Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target

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