Immunology and Immunotherapy of Endometriosis

Abstract

Endometriosis is one of the most common gynecological and systemic diseases, with a remarkable immune background. Patients suffer from pain and fertility reduction. Due to the distinct immune component, an immunotherapeutic approach may gain importance in the future. In endometriosis, shifts in the cell fractions of the immune system are well known. Moreover, hypoxia concomitant with inflammation causes a disturbed immune response. The removal of endometriosis has a therapeutic effect, normalizes the immune disorders, and remains the most effective causative treatment in terms of pain and infertility. A key issue is whether a similar effect can be achieved for fertility with non-invasive immunotherapy where surgery is inadvisable or cannot be performed for various reasons. Numerous immunotherapy trials, including vaccines, were conducted on animals only, although the research is encouraging. Among the promising methods of non-specific immunotherapy is the administration of an ethiodized oil contrast. Moreover, due to the significant successes of immunotherapy in oncology, the possibility of immunotherapy affecting NK cells has been postulated. NK cells are responsible for the surveillance and apoptosis of ectopic cells. Expanding the arsenal of endometriosis treatment by immunotherapy is promising due to the significant contribution of immunological factors and the limitations of current treatment methods.

Inflammation-Related Molecules at the Maternal–Fetal Interface during Pregnancy and in Pathologically Altered Endometrium

“…Endometriosis is caused by hereditary as well as environmental factors [ 99 ]. It affects approximately 190 million women worldwide.…”

“…The local concentration of estrogens and androgens is extremely high compared to peripheral blood concentrations and causes changes in cytokine expression ( Figure 3 ), disrupting the normal function of the endometrium in endometriosis [ 102 , 103 , 104 ]. Released cytokines involved in immune responses and responsible for inflammation are TNF, IL-1, IL-6, IL-8, IL-10, and TGF-B1 [ 99 ]. Other characteristic features of inflammation observed in endometriosis are the infiltration of lymphocytes; synthesis of eicosanoids and metalloproteinases; and atypical changes in the populations of T, B, Treg, and NK lymphocytes.…”

“…Considering their effects on fertility, they have advantages and disadvantages. An improvement in pregnancy rate is offered by the surgical removal of endometriosis lesions or short-term immunotherapy using glucocorticosteroids [ 99 ]. Adhesiolysis enhances the chance of spontaneous pregnancy [ 133 ].…”

The Role of the Immune System in the Development of Endometriosis

“…A promising factor involved in the pathogenesis of endometriosis seems to be immune checkpoint inhibitors, as indicated in very recent literature [13]. It is still uncertain whether disorders of the immune system initiate endometriosis; however, the course of the disease can be affected by modulating its actions [14].…”

Endometrial cytokines, endometriosis and infertility: a deeper dive into the endometrial immune microenvironment

“…Once validated, these findings will indeed further define the role of uNK in endometriosis patients, which will be a step forward toward a better characterization of the different disease phenotypes. Moreover, uNK cell modification could be a possible therapeutic target for a subset of endometriosis patients (4).…”