Endometriosis: the immune pathway opens new treatment avenues
Endometriosis is linked to disruptions of innate and adaptive immunity, worsened by endometrial dysbiosis, which promotes inflammation and lesion progression. Could this be an avenue for new therapeutic strategies?
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About this article
In recent years, growing attention has been paid to immune disorders in endometriosis, a condition that affects about 1 in 10 women.
10% Endometriosis is one of the most prevalent gynecological diseases, affecting up to 10% of women of reproductive age worldwide... ²
190 million which represents 190 million women, worldwide. ²
These women show several disruptions in innate immunity (rapid, non-specific, without immune memory) and adaptive immunity (antigen-specific). Hence, the relevance of this narrative review, which draws on 198 publications to summarize current knowledge on the immunopathogenesis of endometriosis. 1
Disruptions in innate and adaptive immunity
The literature confirms that the pathogenesis of endometriosis appears to be driven by disruptions affecting both innate immunity (macrophages, neutrophils, NK cells, complement) and adaptive immunity (T and B lymphocytes). This is true across every stage of development and for all forms of the condition (ovarian, deep infiltrating, extra-genital or adenomyosis).
1st Endometriosis is the leading cause of subfertility. ²
4 - 12 years Currently, the average time to diagnosis is between 4 and 12 years. ²
Innate immune cells create an inflammatory microenvironment that supports the survival of ectopic endometrial cells, while dysfunction in adaptive immunity (reduced cytotoxic T-cell activity, Treg-mediated immune tolerance) allows these cells to escape elimination once implanted.
Together, these two mechanisms promote the implantation of endometriotic lesions, their growth, angiogenesis and progressive tissue damage, maintaining a self-perpetuating inflammatory cycle.
What is the role of the endometrial microbiota?
In women with endometriosis, dysbiosis of the endometrial microbiota is observed: an increase in pathogenic bacteria such as Escherichia coli, Shigella and Streptococcus, and a decrease in protective Lactobacillus species.
Vaginal microbiome may predict the severity of endometriosis
This dysbiosis is associated with activation of the complement system, which may enhance local inflammation and promote the attachment of endometrial cells to the peritoneal mesothelium.
Due to chronic inflammation, macrophages that should be in “destruction” mode (M1 phenotype) shift to an anti-inflammatory and healing mode (M2 type). Instead of eliminating displaced endometrial cells, they “calm” the immune response, support tissue repair and promote lesion survival.
Therapeutic avenues
Beyond advancing knowledge, understanding the mechanisms of endometriosis immunopathogenesis paves the way for targeted immunotherapy. Goal: directly modulate dysfunctional immune components.
Among the strategies under study are immunomodulators, cytokine/chemokine inhibitors, gene therapy, nanotechnology, immune checkpoint targeting (PD-1/PD-L1, CTLA-4) and therapies guided by macrophages and NK cells. Probiotics may also play an important role, as oral administration of Lactobacillus gasseri activates NK cells and reduces lesion size in a mouse model.
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