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

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34539624", "kind": "science-record", "revision": 7, "content_hash": "sha256:1ce10aadce4de06dc3412b9b2a2deeea468e62dc8fdac8a09295e88e4c3a5970", "created_at": "2026-11-01T15:41:53Z", "updated_at": "2026-11-01T22:04:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of the Signatures of Infiltrating Immune Cells in the Eutopic Endometrium Endometria of Women With Endometriosis.", "doi": "10.3389/fimmu.2021.671201", "pmid": "34539624", "authors": ["Xiang-Guang Wu", "Jin-Jiao Chen", "Hui-Ling Zhou", "Yu Wu", "Fei Lin", "Jing Shi", "Hong-Zhen Wu", "Hai-Qun Xiao", "Wei Wang"], "journal": "Frontiers in immunology", "year": 2021, "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.", "claims": [{"id": "claim-method", "statement": "Data were assessed by the Wilcoxon rank-sum test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34539624", "locator": "sections[12] \"The Signatures of Infiltrating Immune Cells in the Eutopic Endometria of Women With Endometriosis\" paragraph 3", "quote": "Data were assessed by the Wilcoxon rank-sum test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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immune cell subsets in the endometrium with or without endometriosis estimated by CIBERSORT.", "structure": {"pmcid": "PMC8446207", "section_index": 12, "section_title": "The Signatures of Infiltrating Immune Cells in the Eutopic Endometria of Women With Endometriosis", "row_count": 11, "column_count": 4}, "table": {"label": "Table 2", "caption": "The proportions of 10 major infiltrating immune cell subsets in the endometrium with or without endometriosis estimated by CIBERSORT.", "rows": [["Types of immune cells", "Eutopic (Mean ± SD)", "Normal (Mean ± SD)", "P values"], ["Plasma.cells", "0.0607 ± 0.0524", "0.0520 ± 0.0329", "0.4228"], ["T.cells.CD8", "0.1659 ± 0.0968", "0.1086 ± 0.0939", "0.0033"], ["T.cells.follicular.helper", "0.0502 ± 0.0311", "0.0349 ± 0.0232", "0.0086"], ["T.cells.regulatory (Tregs)", "0.0476 ± 0.4356", "0.0484 ± 0.0384", "0.0720"], ["NK.cells.activated", "0.2130 ± 0.0915", "0.1650 ± 0.0609", "0.0029"], ["Monocytes", "0.0333 ± 0.0296", "0.0193 ± 0.0191", 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"Validation of the Density and Distribution of Endometrial Immune Cells in Clinical Samples", "row_count": 5, "column_count": 4}, "table": {"label": "Table 3", "caption": "The proportions of infiltrating immune cells in the endometrium between normal and endometriosis.", "rows": [["Types of immune cells", "Eutopic (Mean ± SD)", "Normal (Mean ± SD)", "P values"], ["CD8+ T cells", "0.2292 ± 0.0591", "0.1790 ± 0.0562", "0.0132"], ["CD56+ NK cells", "0.1686 ± 0.0745", "0.1163 ± .0560", "0.0227"], ["CD117+ Mast cells", "0.1026 ± 0. 0279", "0.1338 ± 0.0538", "0.0718"], ["CD163+ Macrophages", "0.1774 ± 0.0685", "0.2555 ± 0.0588", "0.0003"]], "row_count": 5, "column_count": 4, "numeric_cells": 15, "header_rows": 1, "locator": "section[14]/table-wrap[1]#T3"}}], "gaps": ["asset:data:geo:GSE120103 not downloaded", "asset:data:geo:GSE120103 licence not read", "asset:data:geo:GSE130435 not downloaded", "asset:data:geo:GSE130435 licence not read", "asset:data:geo:GSE25628 not downloaded", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE6364", "GSE25628", "GSE51981", "GSE120103", "GSE130435"], "resolved_accessions": ["GSE6364", "GSE25628", "GSE51981", "GSE120103", "GSE130435"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE6364\nhttps://www.ncbi.nlm.nih.gov/, GSE25628\nhttps://www.ncbi.nlm.nih.gov/, GSE51981\nhttps://www.ncbi.nlm.nih.gov/, GSE120103\nhttps://www.ncbi.nlm.nih.gov/, GSE130435"], "basis": "The paper names GSE6364, GSE25628, GSE51981, GSE120103, GSE130435 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:34539624", "data:geo:GSE120103", "asset:table:pmid:34539624:1", "asset:table:pmid:34539624:2", "asset:table:pmid:34539624:3"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE120103"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:51Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 29680, "completion_tokens": 1906, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:34539624", "type": "paper", "label": "pmid:34539624"}, {"id": "source:pmid:34539624", "type": "manuscript", "label": "PMID 34539624 full text"}, {"id": "data:geo:GSE120103", "type": "dataset", "label": "GEO GSE120103"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34539624", "type": "paper", "label": "pmid:34539624"}, {"id": "source:pmid:34539624", "type": "manuscript", "label": "PMID 34539624 full text"}, {"id": "data:geo:GSE120103", "type": "dataset", "label": "GEO GSE120103"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34539624", "type": "extraction", "used": ["source:pmid:34539624"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE120103", "type": "accession_resolution", "used": ["data:geo:GSE120103"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:34539624", "parent_hash": "sha256:ae974e4c45fd1cbe714a7956e88605511e6aaba6dad571e1aeeeda7e413c908a", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE120103 licence not read", "asset:data:geo:GSE120103 not downloaded", "asset:data:geo:GSE130435 licence not read", "asset:data:geo:GSE130435 not downloaded", "asset:data:geo:GSE25628 licence not read", "asset:data:geo:GSE25628 not downloaded", "asset:data:geo:GSE51981 licence not read", "asset:data:geo:GSE51981 not downloaded", "asset:data:geo:GSE6364 licence not read", "asset:data:geo:GSE6364 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ed for haematoxylin and eosin (HE) staining, immunohistochemistry (IHC) staining, and immunofluorescence stain", "n-embedded endometrial specimens (n = 40) by immunohistochemistry using serial sections. 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