Identification and Validation of the Signatures of Infiltrating Immune Cells in the Eutopic Endometrium Endometria of Women With Endometriosis

Xiang‐Guang Wu, Xiang-Guang Wu, Jin-Jiao Chen, Jin‐Jiao Chen, Hui-Ling Zhou, Huiling Zhou, Yu Wu, Fei Lin, Jing Shi, Hong-Zhen Wu, Hai-Qun Xiao, Wei Wang
Frontiers in immunology · 2021 · vol. 12 , pp. 671201 · doi:10.3389/fimmu.2021.671201 · PMID:34539624 · PMC8446207 · W3196328621
article OA: gold CC0 ⤵ 28 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-10 ⓘ

This study found increased CD8+ T cells and CD56+ NK cells and decreased CD163+ macrophages in the eutopic endometria of women with endometriosis, suggesting a pro-inflammatory immune environment and elevated CD8+ T cells correlating with infertility.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

This study analyzed gene expression data from GEO to characterize the composition, density, and distribution of infiltrating immune cells in eutopic endometrium of women with endometriosis, using CIBERSORT, MCP-counter, and ImmuCellAI, with samples restricted to proliferation and early secretory menstrual phases to reduce menstrual-cycle effects. The authors reported that TNF, IL-17, and MAPK signaling pathways were enriched in endometriosis and that estimated immune cell fractions differed: CD8+ T cells, activated NK cells, and follicular helper T cells were higher, while M2 macrophages and resting mast cells were lower; in GSE120103, elevated CD8+ T cells were associated with infertility (AUC for fertile vs infertile = 0.914), and in clinical specimens (n=40) CD8+ T cells and CD56+ NK cells were higher and CD163+ macrophages lower, yielding AUCs of 0.727 and 0.833 for candidate diagnostic markers. A key limitation is that immune-cell abundance was inferred from bulk transcriptomic deconvolution/estimation methods and then partially validated in a small clinical cohort. This paper is centrally about endometriosis — it focuses on immune-cell signatures in eutopic endometrium of women with endometriosis and links CD8+ T cells with infertility risk.

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Abstract

Endometriosis is an oestrogen-dependent chronic inflammatory process with primary symptoms including dysmenorrhea, chronic pelvic pain, and infertility. The immune environment of the endometrium is essential for successful embryo implantation and ongoing pregnancy. In this study, we assessed the composition, density, and distribution of infiltrating immune cells in the endometria of women with endometriosis. Gene expression profiles of endometrial samples were downloaded from the Gene Expression Omnibus (GEO) database. We found that the TNF signalling pathway, the IL-17 signalling pathway, and the MAPK signalling pathway were significantly enriched in the eutopic endometria of women with endometriosis. The fractions and proportion of infiltrating immune cells were estimated by the CIBERSORT, MCP-counter, and ImmuCellAI methods. We found that the proportions of CD8 + T cells, activated NK cells, and follicular helper T cells were significantly higher in the endometria of women with endometriosis than in the endometria of normal controls, while the proportions of M2 macrophages and resting mast cells were significantly lower in the eutopic endometria. In GSE120103 (n = 36), we found that elevated CD8 + T cells in endometriosis increased the risk of infertility (P = 0.0019). The area under the receiver operating characteristic (ROC) curve (AUC) of CD8 + T cells to distinguish fertile and infertile endometriosis was 0.914. In clinical samples (n = 40), we found that the proportions of CD8 + T cells and CD56 + NK cells were significantly higher in the eutopic endometria of women with endometriosis than in the endometria of normal controls, while the proportion of CD163 + macrophages were lower in the eutopic endometria. The AUCs of CD8 + T cells and CD163 + macrophages were 0.727 and 0.833, respectively, which indicated that CD8 and CD163 were potential diagnostic markers for endometriosis. In conclusion, our results demonstrated that increased CD8 + T cells and CD56 + NK cells and decreased CD163 + macrophages within the eutopic endometria of women with endometriosis reveal a proinflammatory feature in the endometrial immune environment and that elevated CD8 + T cells increase the risk of infertility in women with the disease.

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Condition tags

endometriosischronic_pelvic_paindysmenorrheainfertility

MeSH descriptors

CD8-Positive T-Lymphocytes Endometriosis Endometrium Inflammation Killer Cells, Natural Macrophages Antigens, CD Antigens, CD Antigens, Differentiation, Myelomonocytic Antigens, Differentiation, Myelomonocytic Biomarkers Biomarkers CD163 Antigen CD56 Antigen CD56 Antigen CD8 Antigens CD8 Antigens CD8-Positive T-Lymphocytes Cell Movement Cells, Cultured

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