Immunopathological insights into endometriosis: from research advances to future treatments

Endometriosis is a chronic gynecological disease and a major global concern for women's health. With advancing knowledge of the condition, the classic definition of endometriosis as "endometrium-like tissue outside the uterus" now appears insufficient to explain its pathophysiology, as it overlooks the complex involvement of multiple systems in disease development. Immunological changes have been recognized in endometriosis for decades, and growing evidence substantiates that immunopathological alterations are a hallmark of the disease. Imbalanced immune cell populations and cellular dysfunctions within both the innate and adaptive immune systems, along with aberrant inflammatory cytokines, contribute to the inflammation associated with endometriosis. Moreover, immune cell dysfunctions such as reduced natural killer (NK) cell activity, impaired dendritic cell (DC) maturation and inhibited T cell function via immune checkpoints (ICPs) make the microenvironment also immune-suppressive, facilitating the immune evasion of endometriotic lesions. Endometriosis associated inflammation also sabotages female fertility across multiple stages, including ovarian function, fertilization, embryo development and pregnancy complications. Recognition of the inflammatory and immune-suppressive microenvironment associated with endometriosis leads to the discovery of potential immunotherapeutic targets. Established treatments like non-steroid anti-inflammatory drugs (NSAIDs) and hormone therapies harbor immunomodulatory properties. Other immune-based therapies such as immune cell therapies, cytokine-targeting therapies and immune checkpoint inhibitors (ICIs), which have demonstrated significant efficacy in many chronic inflammatory diseases including cancers, may hold substantial promise as future treatments for endometriosis.