Immune сheckpoints in the context of external genital endometriosis

Endometriosis is a chronic recurrent disease with insufficiently studied pathogenesis. Endometriosis is known to share similar features with tumors. Thus, the outgrowth of endometrium-like tissue outside the uterus is the main feature of this condition. The dysfunction of local immune response is required for cell proliferation and invasion in ectopic sites. The involvement of immune checkpoints is among the mechanisms allowing avoidance of immune surveillance shown for the tumors. Immune checkpoints are presented by proteins expressed on immune cells (most on T cells). The checkpoint binding to its ligand expressed on immune cells leads to its functional inhibition and, thus, facilitates survival of tumor cells. The data about immune checkpoints, e.g., CTLA-4, PD-1, LAG-3, Tim-3, TIGIT, 4-1BB, GITR are summarized in this review. Their ligands (CD80/CD86, PD-1L, Gal-3, Gal-9) are also described. The review article contains information about cells expressing checkpoints and other proteins involved, We also discuss the examples of tumors using such checkpoint-ligand interactions in order to avoid recognition by immune cells. Furthermore, the review describes immune checkpoint inhibitors currently used in cancer therapy. Due to scarce knowledge about endometriosis pathogenesis, the only diagnostics of this condition is laparoscopic surgery with visualization of ectopic loci and histological study of biopsies. The studies of some biomarkers for non-invasive diagnosis of endometriosis, such as CA-125, MCP-1, IL-6, BDNF etc. are also discussed in this review. The authors describe some studies which concern immune checkpoints in the context of endometriosis. Noteworthy an elevated expression of some checkpoints by T cells was found, along with elevated concentration of their soluble forms in blood of women with endometriosis. The review also includes the studies showing significant sensitivity and specificity of immune checkpoint ligand measurement in patients with endometriosis. Hence, investigation of immune checkpoints as a potential mechanism to avoid immune reaction used by endometriotic cells, and its application as a biomarker for non-invasive diagnostics is a promising direction for the further studies. 

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