Expression of programmed death-1 (PD-1) and its ligand PD-L1 is upregulated in endometriosis and promoted by 17beta-estradiol

Wu, Lukanxuan; Lv, Chunzi; Su, Yi-Feng; Li, Chunyan; Zhang, Hui; Zhao, Xinghui; Li, Mingjiang

doi:10.1080/09513590.2018.1519787

Cited by 42 publications

(56 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Considering the above immune regulatory functions of soluble immune checkpoint molecules, it seems that they play a crucial role in the pathogenesis of endometriosis. Recently, the membrane‐bound PD‐1/PD‐L1 expressed by lymphocytes and endometrial tissues were described in endometriosis 17‐19 . In the current study, we hypothesize that soluble immune checkpoint molecules in peripheral circulation and peritoneal fluid will be elevated during endometriosis in infertile women.…”

Section: Introductionmentioning

confidence: 64%

“…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%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 64%

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

View full text Add to dashboard Cite

show abstract

“…The suppressive action of T cells is also dependent on PD-1 expression in Tregs, which is also increased by E2 (171). E2 also increased PD-L1 expression on T cells from the reproductive tract tissues (172,173). This provides another mechanism by which the adaptive component of the TME can have an estrogen dependent effect on the therapeutic efficacy of ICIs.…”

Section: Immune Checkpoint Modulationmentioning

confidence: 95%

Influence of Estrogen on the NSCLC Microenvironment: A Comprehensive Picture and Clinical Implications

2020

View full text Add to dashboard Cite

Lung cancer mortality represents the leading cause of cancer related deaths in the United States and worldwide. Almost half of these deaths occur in female patients, making lung cancer the most common cause of cancer mortality in women with a higher annual mortality rate than breast, uterine, and ovarian cancers combined. The distinct epidemiological, histological and biological presentation of non-small cell lung cancer (NSCLC) in women combined with extensive preclinical data have demonstrated that the female sex hormone β-estradiol (E2) plays an important role in NSCLC tumorigenesis, prognosis, and treatment response. Estrogen receptors are widely expressed on stromal and immune cells, and estrogen-linked signaling pathways are known to be involved in regulating the response of both the innate and adaptive immune system. Immune evasion has been recognized as a "hallmark" of cancer and immunotherapy has re-defined standard of care treatment for NSCLC. Despite these advancements, the low response rates observed in patients treated with immune checkpoint inhibitors has led to a search for mediators of immunosuppression and ways to augment the action of these agents. We focus on emerging data describing sex differences that modulate immunotherapy efficacy in NSCLC, immunosuppressive properties of E2 that lead to a pro-tumor microenvironment (TME), and the translational potential of altering the immune microenvironment by targeting the estrogen signaling pathway. E2-induced modulation affects multiple cell types within the TME, including cancer-associated fibroblasts, tumor infiltrating myeloid cells, and tumor infiltrating lymphocytes, all of which interplay with lung tumor cells via E2 and estrogen receptor engagement, ultimately shaping the TME that may, in part, be responsible for the sex-based disparities observed in NSCLC. An improved understanding of the role of the estrogen pathway in NSCLC anti-cancer immunity may lead to novel therapeutic approaches for altering the TME to improve the efficacy of immunotherapy agents.

show abstract

“…Recently, it has been shown that the expression of both PD-1 and PDL-1 is upregulated in CD4 + and CD8 + T cells and CD19 + B cells from the peripheral blood of patients with endometriosis as compared to control women [118]. The increased expression of PD-1/PDL-1 in CD4 + CD8 + T cells was confirmed by Wu et al [119]. More importantly, the latter authors showed that PD-1/PDL-1 is also expressed in the eutopic endometrium and ectopic endometriotic lesions and that this expression is increased in endometriosis.…”

Section: Expression Of Nk Cell Receptors and Their Ligands In Patimentioning

confidence: 84%

NK Cells as Potential Targets for Immunotherapy in Endometriosis

Ścieżyńska

Komorowski

Soszyńska

et al. 2019

JCM

View full text Add to dashboard Cite

Endometriosis is a common gynecological disease defined by the presence of endometrial-like tissue outside the uterus, most frequently on the pelvic viscera and ovaries, which is associated with pelvic pains and infertility. It is an inflammatory disorder with some features of autoimmunity. It is accepted that ectopic endometriotic tissue originates from endometrial cells exfoliated during menstruation and disseminating into the peritoneum by retrograde menstrual blood flow. It is assumed that the survival of endometriotic cells in the peritoneal cavity may be partially due to their abrogated elimination by natural killer (NK) cells. The decrease of NK cell cytotoxic activity in endometriosis is associated with an increased expression of some inhibitory NK cell receptors. It may be also related to the expression of human leukocyte antigen G (HLA-G), a ligand for inhibitory leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) receptors. The downregulated cytotoxic activity of NK cells may be due to inhibitory cytokines present in the peritoneal milieu of patients with endometriosis. The role of NK cell receptors and their ligands in endometriosis is also confirmed by genetic association studies. Thus, endometriosis may be a subject of immunotherapy by blocking NK cell negative control checkpoints including inhibitory NK cell receptors. Immunotherapies with genetically modified NK cells also cannot be excluded.

show abstract

Expression of programmed death-1 (PD-1) and its ligand PD-L1 is upregulated in endometriosis and promoted by 17beta-estradiol

Cited by 42 publications

References 26 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

Influence of Estrogen on the NSCLC Microenvironment: A Comprehensive Picture and Clinical Implications

NK Cells as Potential Targets for Immunotherapy in Endometriosis

Contact Info

Product

Resources

About