Emerging Mechanisms of NK Cell Dysfunction in Endometriosis: The Role of Autophagy, Metabolism, Cytokines, Exosomes, and Trogocytosis

ABSTRACT Endometriosis (EMS) is a persistent, inflammatory condition that relies on estrogen and is distinguished by the proliferation of endometrial tissue outside the confines of the uterus. The impact on the well‐being of individuals affected can be significant, as it is linked to pelvic pain and reduced fertility in women of reproductive age. Over 30 years have passed since initially discovering a malfunction in the activity of natural killer (NK) cells in individuals with EMS. Several aspects that contribute to NK cell dysfunction have been explored by researchers over the years, such as the upregulation of inhibitory receptors, downregulation of activating receptors, and the exhaustion process. Nonetheless, there are still many aspects that have yet to be identified. The objective of this review is to explore whether there is a connection between mechanisms that have not yet been explored and the malfunctioning of EMS‐derived NK cells. Autophagy, metabolism, trogocytosis, tunneling nanotubes (TNT), and exosomes are among the factors that play a role in these processes. The primary objective of this publication is to provide valuable insights for future research on NK cells, with the aim of enhancing our understanding of the disease's causes and identifying more effective targets for immunotherapy.