Endometriosis is a chronic inflammatory disorder, characterized by the presence of endometrial cells outside the uterine cavity. An increasing number of studies correlate the immune system with endometriosis, particularly NK receptors (NKR), which have been suggested to play an essential role in the pathogenesis of the disease. This systematic review aims to enlighten the role of NKR in endometriosis. A literature search was performed independently by two reviewers, to identify studies assessing the role of NKR in endometriosis. In total, 18 studies were included. Endometriosis pathogenesis seems to be marked by the overexpression of NK inhibitor receptors (KIRS), namely, CD158a+, KIR2DL1, CD94/NKG2A, PD-1, NKB1, and EB6, and inhibiting ligands such as PD-L1, HLA-E, HLA-G, and HLA-I. Concurrently, there is a decrease in NK-activating receptors and natural cytotoxicity receptors (NCRs), such as NKp46, NKp30, and NKG2D. The immune shift from NK surveillance to NK suppression is also apparent in the greater relative number of ITIM domains compared with ITAM domains in NKRs. In conclusion, NK receptor activity seems to dictate the immunocompetency of women to clear endometriotic cells from the peritoneal cavity. Future research could explore NKRs as therapeutic targets, such as that which is now well established in cancer therapy through immunotherapy.

Endometriosis, a debilitating condition, affects one in ten women of reproductive age. Its pathophysiology remains unclear, though deficiencies in immune surveillance are thought to create an environment conducive to the evasion of ectopic endometrial cells from the immune system. Our research explores the immunological impact of endometriosis both locally and systemically, emphasizing natural killer (NK) and T cell subpopulations. We incorporated 62 female patients who underwent laparoscopic surgery; of those, 47 had endometriosis, and 15 were controls. We collected peritoneal fluid (PF) and peripheral blood (PB) samples which were tagged with monoclonal antibodies and subsequently scrutinized using flow cytometry. Our findings revealed significant differences in immunological profiles based on demographic factors and symptomatology. In the endometriosis cohort, there was an increase in PB CD56^HiCD16^dim and PF CD8⁺ CD56^dimCD16^Hi NK cells. CD16⁺ CD4 T cell levels were significantly lower in the PB of endometriosis patients who smoke. Individuals with more severe disease displayed significantly higher levels of PB CD16⁺ CD8 T cells, which also increased in those with non-menstrual pelvic pain. Dysmenorrhea severity correlated with a progressive increase in PF CD8⁺ CD56^dimCD16^Hi NK cells. These variations in specific lymphocyte subsets, namely, within NK and T cells, suggest potential immunological mechanisms in the evolution and clinical presentation of endometriosis.