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J Clin Med. 2019 Sep 14;8(9). pii: E1468. doi: 10.3390/jcm8091468.

NK Cells as Potential Targets for Immunotherapy in Endometriosis.

Author information

1
Department of Histology and Embryology, Medical University of Warsaw, Chałubińskiego 5, 02-004 Warsaw, Poland. asciezynska@wum.edu.pl.
2
Laboratory for Experimental Immunology, Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland. asciezynska@wum.edu.pl.
3
Laboratory for Experimental Immunology, Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland. michalpiotrkomorowski91@gmail.com.
4
Laboratory for Experimental Immunology, Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland. marta.soszynska@onet.eu.
5
Department of Histology and Embryology, Medical University of Warsaw, Chałubińskiego 5, 02-004 Warsaw, Poland. jacek.malejczyk@wum.edu.pl.
6
Laboratory for Experimental Immunology, Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland. jacek.malejczyk@wum.edu.pl.

Abstract

Endometriosis is a common gynecological disease defined by the presence of endometrial-like tissue outside the uterus, most frequently on the pelvic viscera and ovaries, which is associated with pelvic pains and infertility. It is an inflammatory disorder with some features of autoimmunity. It is accepted that ectopic endometriotic tissue originates from endometrial cells exfoliated during menstruation and disseminating into the peritoneum by retrograde menstrual blood flow. It is assumed that the survival of endometriotic cells in the peritoneal cavity may be partially due to their abrogated elimination by natural killer (NK) cells. The decrease of NK cell cytotoxic activity in endometriosis is associated with an increased expression of some inhibitory NK cell receptors. It may be also related to the expression of human leukocyte antigen G (HLA-G), a ligand for inhibitory leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) receptors. The downregulated cytotoxic activity of NK cells may be due to inhibitory cytokines present in the peritoneal milieu of patients with endometriosis. The role of NK cell receptors and their ligands in endometriosis is also confirmed by genetic association studies. Thus, endometriosis may be a subject of immunotherapy by blocking NK cell negative control checkpoints including inhibitory NK cell receptors. Immunotherapies with genetically modified NK cells also cannot be excluded.

KEYWORDS:

NK cell receptors; endometriosis; endometriotic cells; immune checkpoint; immunotherapy; major histocompatibility complex class I; natural killer (NK) cells

PMID:
31540116
DOI:
10.3390/jcm8091468
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Conflict of interest statement

Authors Contribution: Conceptualization, A.Ś., J.M.; literature search & acquisition, M.K., M.S., A.Ś., J.M.; writing—original draft preparation, M.K., M.S., A.Ś., J.M.; writing—review & editing, A.Ś., J.M.

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