NK Cell Therapy in Endometriosis Treatment

Endometriosis is a common gynecological disorder in women, affecting hormonal balance. It afflicts approximately 10% of women worldwide, roughly 200 million individuals [1,2]. This condition occurs when endometrial cells are found outside the uterus. Common locations for endometrial tissue include the pelvic region (peritoneum), ovaries, fallopian tubes, and rectum. Endometrial tissue often comprises endometrial stromal cells, endometrial epithelial cells, red blood cells, and hemosiderin-laden macrophages. The impact on women’s quality of life and families, especially psychologically, is substantial. Therefore, therapies to address this issue are crucial. NK cell therapy is emerging as a ray of hope for women with endometriosis.

Overview of Endometriosis

Endometriosis induces pelvic inflammation and commonly presents symptoms such as menstrual cramps, chronic pelvic pain, painful urination, bowel movement disorders, infertility, and miscarriages [3,4,5]. Current treatments include pain relief medication, hormonal regulation, or surgery [1,2,6]. Endometriosis severely affects women’s overall health, yet there is no specific treatment available.

Endometriosis is a complex disorder originating from multiple factors such as genetics, immune responses, and environmental influences, yet these elements have not been conclusively defined [1,7]. The origin and mechanism behind the development of endometrial lesions remain a debated issue [7,8]. One suggested cause for the formation of endometrial tissue is the shedding of endometrial cells during menstruation, which then retrograde into the peritoneal cavity via the fallopian tubes [9].

Changes in NK Cell Activity in Endometriosis Patients

This condition manifests through immune reactions and abnormal cellular activities, including peritoneal infection, macrophage activation, lymphocyte and NK cell dysfunction, and cytokine dysregulation [10-12].

Specific dysregulation in NK cell activity involves both inhibition and reduced survival rates. The development of endometrial tissue is closely linked to decreased NK cell activity [13-16]. NK cell activity is closely related to immune responses in the body. NK cell activity depends on immune checkpoint molecules [17-19]. These checkpoints signal the invasion of foreign cells, such as cancer cells. When NK cell activity is inhibited, it creates conditions conducive to the development of endometrial tissue within the uterus. Figure 1 illustrates the role of NK cells in the immune system. When NK cells’ activity is suppressed, immune balance is disrupted, facilitating the formation of endometrial tissue.

Figure 1: NK cell activity under normal and suppressed conditions resulting in endometrial tissue formation

The first report on inhibited NK cell activity and reduced survival rates in endometriosis patients was presented by Oosterlynck and colleagues. They used K562 cells (a sensitive NK cell line) to measure NK cell activity in endometriosis patients and compared it with non-affected individuals [20]. The results indicated significantly lower NK cell activity against K562 cells in women with endometriosis in both peripheral blood and peritoneal fluid. CD56+ and CD16+ ratios, specific markers for NK cell expression, were also significantly reduced in affected individuals [21]. A recent study on autologous NK cell therapy in endometriosis patients was conducted at the People’s Hospital in Tianjin, China.

This study is in its Phase 1 trial involving 60 diagnosed stage III-IV endometriosis patients. Half of the participants will undergo standard treatment with gonadotropin-releasing hormone therapy combined with Western medicine supplementation, while the other half will receive similar treatment combined with autologous NK cell therapy. Parameters will be evaluated to compare the effectiveness of the two treatments, including side effects during treatment, endocrine hormone levels, pain levels, and pregnancy rates. Current results suggest that NK therapy yields positive effects for patients. The clinical trial ID is NCT03948828. The study indicates that NK cell activity decisively determines the immune ability to eliminate endometrial lesions. Inhibiting NK cell activity may favor the development of endometrial tissue, causing growth, proliferation, and immune escape, contributing to tissue damage.

Further research detailing NK cell roles in endometriosis will help develop new therapeutic strategies, improving patients’ quality of life and resolving infertility issues caused by this condition. Future exploration could focus on NK cell inhibition targets as treatment objectives, counteracting their overexpression in endometriosis.

NK cells are considered a protective barrier and an alarm system against abnormal cell invasion. When NK cell activity decreases, cells shed in the uterus will form tissue, causing pain for affected women. The activity and survival rate of NK cells can serve as a diagnostic method for endometriosis in women. More research is required to assess the relationship between NK cell activity and the formation of endometrial tissue, the cause of endometriosis.

References:

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