Immunotherapy for endometrisosis: Will it be possible?

Evidences point to modifications on Natural Killer (NK) cells of the immune system could have a potential therapeutic role in endometriosis

Key Points

Background:

• There is substantial evidence that endometriosis may be related to the alterations of the immune system.
• There are clues such as peritoneal infiltration of immune cells, the activation of macrophages, abnormal lymphocyte responses and abolished natural killer (NK) cell cytotoxicity besides excess proinflammatory and regulatory cytokine production. 

Highlights:

• The survival and growth of endometriotic cells in the peritoneal cavity is related to their abolished recognition and elimination by immune cells, especially by phagocytic monocytes and NK cells. 
• Endometriosis may be associated with downregulated NK cytotoxicity, hence peritoneal and endometriotic tissues in women with endometriosis may harbor inhibitory cytokines interfering with normal immunity yo inhibit NK cell cytotoxicity. 

What's Done Here?

• The authors have made a comprehensive review of possible roles of NK cells related to the pathophysiology of endometriosis

Conclusions: 

• There is evidence that endometriosis is associated with the downregulation of NK cell cytotoxicity.
• Functional and genetic studies reveal that possible mechanisms include defective lysis of ectopic endometriotic cells. 
• The upregulation of inhibitory NK cell receptors and the downregulation of stimulatory ones in endometriosis may be related to the activity of some local inhibitory factors also.
• There are promising study topics such as inhibition of NK cell cytotoxicity reversed by anti-inhibitory cytokine therapy or the inhibition of NK cells might be overcome by some stimulatory cytokines.

Lay Summary

This comprehensive review on the pathophysiology of endometriosis by Dr. Sciezynska and colleagues from the Medical University of Warshaw, Poland appeared in the September 2019 issue of "Journal of Clinical Medicine".

Endometriosis is a considerable health issue where current treatment strategies are mainly limited to analgesic or hormonal therapy and surgery. Currently, there is substantial evidence suggesting endometriosis may be related to the altered immunity, both local and systemic. Peritoneal infiltration of immune cells, activation of macrophages, abnormal lymphocyte responses and diminished natural killer (NK) cell cytotoxicity and excess proinflammatory and regulatory cytokine production are majör topics of current investigations. The survival and growth of endometriotic cells in the peritoneal cavity seems to be the result of a failure of mainly phagocytic monocytes and NK cells. There is cumulative evidence that endometriosis may also be associated with the downregulation of NK cytotoxicity.

Peritoneal environment and endometriotic tissues in women with endometriosis may harbor inhibitory cytokines interfering with normal immunity so that NK cell cytotoxicity may be inhibited. Functional and genetic studies reveal that possible mechanisms also include defective lysis of ectopic endometriotic cells. The upregulation of inhibitory NK cell receptors and the downregulation of stimulatory ones in endometriosis may be related to the activity of some local inhibitory factors.

These promising study topics may yield possible therapeutics such as enhancing NK cell cytotoxicity by anti-inhibitory cytokines or stimulatory cytokines.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/31540116