Ovarian endometrioma infiltrating neutrophils orchestrate immunosuppressive microenvironment

Abstract Background Ovarian endometrioma (EM) lesions not only have overwhelmed the amount of infiltrating immune cells but also display immunosuppressive phenotype. The close relationship between neutrophils and the pathogenesis of endometriosis has been demonstrated. The present study aims to eluc...

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Bibliographic Details
Main Authors: Hua Xu, Jing Zhao, Jiaqi Lu, Xiaoxi Sun
Format: Article
Language:English
Published: BMC 2020-04-01
Series:Journal of Ovarian Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13048-020-00642-7
Description
Summary:Abstract Background Ovarian endometrioma (EM) lesions not only have overwhelmed the amount of infiltrating immune cells but also display immunosuppressive phenotype. The close relationship between neutrophils and the pathogenesis of endometriosis has been demonstrated. The present study aims to elucidate whether or not neutrophils are involved in the regulation of immunosuppressive microenvironment in ovarian endometrioma. Methods Immunochemistry (IHC) and flow cytometry analysis (FACS) were conducted to measure CD66b expression in ovarian endometrioma samples from EM patients. The correlation between percentage of CD66b and PD1 + CD8+, TIM3 + CD8+, CTLA4 + CD8+, IFN-γ + CD8+ of CD45+ cells were analyzed. Neutrophil survival and PD-L1 expression were determined under the stimulations of ovarian endometrioma conditional supernatants (OECS). Finally, CD8+ T cell’s proliferation and IFN-γ expression were detected under co-cultured with OECS cultured neutrophils stimulated with the α-CD3/α-CD28 antibody. Results IHC and FACS results revealed correlation between the counts of neutrophils and the severity of ovarian endometrioma. The percentage of CD66b + cells was positively correlated with PD1 + CD8+, TIM3 + CD8+ and CTLA4 + CD8+ of CD45+ cells in ovarian endometrioma. OECS promoted neutrophils’ survival and enhanced PD-L1 expression. OECS cultured neutrophils inhibited proliferation and activity of autologous T cells. Conclusions Neutrophils play a crucial role in the progression of ovarian endometrioma by orchestrated the immunosuppressive microenvironment under the PD-1/PD-L1 axis.
ISSN:1757-2215