The role of CD8+ T cells in endometriosis: a systematic review

BackgroundEndometriosis is a chronic disease affecting 6–10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in les...

Full description

Bibliographic Details
Main Authors: Ana Kisovar, Christian M. Becker, Ingrid Granne, Jennifer H. Southcombe
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1225639/full
_version_ 1797783214773764096
author Ana Kisovar
Christian M. Becker
Ingrid Granne
Jennifer H. Southcombe
author_facet Ana Kisovar
Christian M. Becker
Ingrid Granne
Jennifer H. Southcombe
author_sort Ana Kisovar
collection DOAJ
description BackgroundEndometriosis is a chronic disease affecting 6–10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in lesion clearance in other pathologies, yet their function in endometriosis is unknown. We systematically evaluated the literature on the CD8 T in peripheral blood and endometriosis-associated tissues to determine the current understanding of their pathophysiological and clinical relevance in the disease and associated conditions (e.g. infertility and pelvic pain).MethodsFour databases were searched (MEDLINE, EMBASE, Web of Science, CINAHL), from database inception until September 2022, for papers written in the English language with database-specific relevant terms/free-text terms from two categories: CD8 T cells and endometriosis. We included peer-reviewed papers investigating CD8 T cells in peripheral blood and endometriosis-associated tissues of patients with surgically confirmed endometriosis between menarche and menopause, and animal models with oestrous cycles. Studies enrolling participants with other gynaecological pathologies (except uterine fibroids and tubal factor infertility used as controls), cancer, immune diseases, or taking immune or hormonal therapy were excluded.Results28 published case-control studies and gene set analyses investigating CD8 T cells in endometriosis were included. Data consistently indicate that CD8 T cells are enriched in endometriotic lesions in comparison to eutopic endometrium, with no differences in peripheral blood CD8 T populations between patients and healthy controls. Evidence on CD8 T cells in peritoneal fluid and eutopic endometrium is conflicting. CD8 T cell cytotoxicity was increased in the menstrual effluent of patients, and genomic analyses have shown a clear trend of enriched CD8 T effector memory cells in the eutopic endometrium of patients.ConclusionLiterature on CD8 T cells in endometriosis-associated tissues is inconsistent. Increased CD8 T levels are found in endometriotic lesions, however, their activation potential is understudied in all relevant tissues. Future research should focus on identifying clinically relevant phenotypes to support the development of non-invasive diagnostic and treatment strategies.Systematic Review RegistrationPROSPERO identifier CRD42021233304
first_indexed 2024-03-13T00:22:53Z
format Article
id doaj.art-112b908108ad4bc792bc85380cf5cf1b
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-03-13T00:22:53Z
publishDate 2023-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-112b908108ad4bc792bc85380cf5cf1b2023-07-11T11:33:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.12256391225639The role of CD8+ T cells in endometriosis: a systematic reviewAna KisovarChristian M. BeckerIngrid GranneJennifer H. SouthcombeBackgroundEndometriosis is a chronic disease affecting 6–10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in lesion clearance in other pathologies, yet their function in endometriosis is unknown. We systematically evaluated the literature on the CD8 T in peripheral blood and endometriosis-associated tissues to determine the current understanding of their pathophysiological and clinical relevance in the disease and associated conditions (e.g. infertility and pelvic pain).MethodsFour databases were searched (MEDLINE, EMBASE, Web of Science, CINAHL), from database inception until September 2022, for papers written in the English language with database-specific relevant terms/free-text terms from two categories: CD8 T cells and endometriosis. We included peer-reviewed papers investigating CD8 T cells in peripheral blood and endometriosis-associated tissues of patients with surgically confirmed endometriosis between menarche and menopause, and animal models with oestrous cycles. Studies enrolling participants with other gynaecological pathologies (except uterine fibroids and tubal factor infertility used as controls), cancer, immune diseases, or taking immune or hormonal therapy were excluded.Results28 published case-control studies and gene set analyses investigating CD8 T cells in endometriosis were included. Data consistently indicate that CD8 T cells are enriched in endometriotic lesions in comparison to eutopic endometrium, with no differences in peripheral blood CD8 T populations between patients and healthy controls. Evidence on CD8 T cells in peritoneal fluid and eutopic endometrium is conflicting. CD8 T cell cytotoxicity was increased in the menstrual effluent of patients, and genomic analyses have shown a clear trend of enriched CD8 T effector memory cells in the eutopic endometrium of patients.ConclusionLiterature on CD8 T cells in endometriosis-associated tissues is inconsistent. Increased CD8 T levels are found in endometriotic lesions, however, their activation potential is understudied in all relevant tissues. Future research should focus on identifying clinically relevant phenotypes to support the development of non-invasive diagnostic and treatment strategies.Systematic Review RegistrationPROSPERO identifier CRD42021233304https://www.frontiersin.org/articles/10.3389/fimmu.2023.1225639/fullCD8T cellendometriosisendometriumperitoneal fluid
spellingShingle Ana Kisovar
Christian M. Becker
Ingrid Granne
Jennifer H. Southcombe
The role of CD8+ T cells in endometriosis: a systematic review
Frontiers in Immunology
CD8
T cell
endometriosis
endometrium
peritoneal fluid
title The role of CD8+ T cells in endometriosis: a systematic review
title_full The role of CD8+ T cells in endometriosis: a systematic review
title_fullStr The role of CD8+ T cells in endometriosis: a systematic review
title_full_unstemmed The role of CD8+ T cells in endometriosis: a systematic review
title_short The role of CD8+ T cells in endometriosis: a systematic review
title_sort role of cd8 t cells in endometriosis a systematic review
topic CD8
T cell
endometriosis
endometrium
peritoneal fluid
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1225639/full
work_keys_str_mv AT anakisovar theroleofcd8tcellsinendometriosisasystematicreview
AT christianmbecker theroleofcd8tcellsinendometriosisasystematicreview
AT ingridgranne theroleofcd8tcellsinendometriosisasystematicreview
AT jenniferhsouthcombe theroleofcd8tcellsinendometriosisasystematicreview
AT anakisovar roleofcd8tcellsinendometriosisasystematicreview
AT christianmbecker roleofcd8tcellsinendometriosisasystematicreview
AT ingridgranne roleofcd8tcellsinendometriosisasystematicreview
AT jenniferhsouthcombe roleofcd8tcellsinendometriosisasystematicreview