Abstract
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.
Highlights
Endometriosis is a common estrogen-dependent benign gynecological disorder affecting approximately 10% of women in their reproductive age which corresponds to 200 million women worldwide [1,2]
A decreased natural killer (NK) cell activity in patients with endometriosis was reported for the first time by Oosterlynck et al who found lowered cytotoxicity of NK cells against K562 cells both in the peripheral blood and the peritoneal fluid [68]
The analysis of NK cells from peripheral blood and peritoneal fluid from women with endometriosis did not reveal any change of expression of CD94 (KLRD1) [99]
Summary
Endometriosis is a common estrogen-dependent benign gynecological disorder affecting approximately 10% of women in their reproductive age which corresponds to 200 million women worldwide [1,2]. The development of ectopic endometriotic lesions may involve the participation of endometrial stem/progenitor cells [28] as well as may be facilitated by epithelial-to-mesenchymal transition [29]. The evidence accumulates that endometriosis may be associated with downregulated NK cell cytotoxicity [19,30,31,32] The mechanisms of this abrogation are still poorly understood. Abrogated elimination of shed endometrial cells in the course of endometriosis may be associated with the activation of some checkpoint molecule pathways (Figure 1). The identification of checkpoints responsible for downregulated NK cell activity in the course of endometriosis may be useful for the identification of new possible therapeutic targets. Inhibitory Natural Killer (NK) Cell Receptors KIR2DL1 KIR2DL2/3 KIR3DL1 KIR3DL2 LILRB1
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