Expression And Significance Of PD-L1 And PI3K/PTEN Pathway In Adenomyosis

BackgroundAdenomyosis(AM)is one of the most common gynecological benign diseases among women of childbearing age,Chronic pelvic pain,progressive dysmenorrhea and abnormal uterine bleeding are the clinical symptoms of adenomyosis.These symptoms affect the patients’ physical and mental health seriously,also,they can have an impact on a patient’s quality of life.Numbers of hypotheses come forward to explain its origin,such as theories of basal intimal invagination,epithelial metaplasia,lymphatic and venous dissemination,etc.Besides,heredity,immunity and hormones also affect the development of adenomyosis,but pathogenesis of adenomyosis is still unclear.In addition,numerous studies have shown that adenomyosis is closely related to cellular immunity.PD-L1(Programmed death-Ligand 1,B7-H1)is the major ligand of Programmed death-1.PD-L1 is immune cells:such as T cells,B cells,NK cells,etc,also expressed on non-immunologic cells,immunocyte activation affects the expression of PD-L1.In healthy organisms,activation of PD-1/PD-L1 pathway can minimize the damage caused by the body’s immune response to surrounding tissues and prevent autoimmune diseases.Abnormal activation of various intracellular signaling pathways involved PI3K/Akt/mTOR pathway is present in AM.The PI3K/Akt pathway plays a role in inhibiting apoptosis,promoting proliferation and differentiation in cells by affecting the activation state of downstream molecules.PTEN is a tumor suppressor gene.It can inhibit tumorigenesis and development through allelic mutation,gene deletion and promoter methylation.Studies have shown that the PTEN gene is deleted in melanoma and the PD-L1 is overexpressed.Activation of PI3K/Akt/mTOR pathway or deletion of PTEN is associated with highly expression of PD-L1 in tumors such as melanoma,glioma,and lung cancer.We proposed assumption that PD-L1 and PI3K are overexpressed in AM,PTEN is lossed in AM,and the expression of PTEN may regulated by PD-1/PD-L1 inhibitor.MethodsTo test these assumption,we used immunofluorescence technique and western blot to examine the expression of PD-LI、PI3K and PTEN in endometrial tissues,endometrial tissues were collected from reproductive age women with AM(n=15)as well as control group(n=15).We also explored their expression in EECs,that were treated with or without PD-1/PD-L1 inhibitor.Results1.Compared with the endometrium of women in contorls,PD-L1,PI3K protein were overexpressed in AM;PTEN was expressed at lower level in AM;2.PTEN expression was upregulated by PD-1/PD-L1 ihibitor in EECs in AM.Conclusion1.PD-1/PD-L1 and PI3K/PTEN signaling pathways are over-activated in AM.The role of PI3K/PTEN pathway in AM may regulated by PD-L1;2.PD-1/PD-L1 inhibitor can up-regulate the expression of PTEN in EECs of adenomyosis by blocking the interaction between PD-1 and PD-L1;3.Providing a new direction for immunotherapy of adenomyosis.