A higher number of exhausted local PD1+, but not TIM3+, NK cells in advanced endometriosis.

Endometriosis (EMT) is a chronic inflammatory disease characterized by the presence and growth of endometrial-like glandular epithelial and stromal cells outside the uterus. Natural Killer (NK) cell dysfunction/exhaustion has been shown in patients with EMT. In this case-control study, we compared the frequency of exhausted PD-1 or TIM-3 positive NK cells in peripheral blood (PB) and peritoneal fluid (PF) of women with advanced endometriosis to control fertile women. PB and PF were collected from women aged 25-40 who underwent the laparoscopic procedure, including 13 stages III/IV endometriosis and 13 control samples. Multicolor flowcytometry was used to compare the frequency of PD-1 or TIM-3 positive NK (CD3- CD56+ ) cells in PB and PF of two groups. We demonstrated a higher percentage of PD-1+ NK cells in the peritoneal fluid of patients with endometriosis rather than controls (P-value = 0.039). This significance was related to stage IV of endometriosis (P-value = 0.047). We can not show any significant difference in the number of PD-1 or TIM-3 positive NK cells in peripheral blood. Our results suggest a local exhausted NK cell response in endometriosis that can be a leading factor in the endometriosis pathogenesis.