{"paper_id":"b00db151-0da0-48c3-ac4e-c771e328d496","body_text":"Abstract\nBackground\nEndometriosis is a prevalent estrogen-dependent inflammatory disorder that compromises women’s quality of life and fertility through chronic pelvic pain, inflammation, and reproductive dysfunction. Current clinical management remains largely palliative, with high recurrence rates and limited disease-modifying options. Evidence emerging over the past five years supports immune escape as a lesion-centered framework for understanding disease persistence and recurrence, in which ectopic lesions survive within an immune-active but clearance-deficient niche.\nMethods\nThis narrative review synthesizes recent mechanistic and translational evidence on immune escape in endometriosis. We organize the literature into a lesion-centered mechanistic hierarchy encompassing lesion-derived cues, defective phagocytic clearance, impaired cytotoxic surveillance, tolerogenic immune priming, checkpoint-mediated protection, and lesion-supportive inflammatory remodeling. We also evaluate emerging immune-reprogramming strategies, including hormone-sparing immunomodulation, nanotechnology-enabled lesion-targeted delivery, and selected concepts adapted from oncology immunotherapy.\nResults\nAvailable studies indicate that lesion-derived inflammatory, metabolic, endocrine, and stromal signals reprogram innate and adaptive immune responses. These changes impair macrophage-mediated clearance, restrain NK-cell and CD8⁺ T-cell cytotoxic functions, alter dendritic-cell-mediated priming and CD4⁺ T-cell regulation, activate inhibitory checkpoint pathways, and redirect inflammation toward angiogenesis, fibrosis, pain sensitization, and local immune tolerance. Together, these processes generate an inflamed yet clearance-deficient niche that may support lesion establishment and persistence. Preclinical immune-reprogramming approaches have shown potential to restore clearance or rebalance pathogenic immune circuits, while nanotechnology-based platforms may improve lesion-local exposure and reduce systemic effects. However, clinical evidence remains limited, and oncology-derived strategies require careful adaptation to the benign, estrogen-dependent, and fertility-relevant context of endometriosis.\nConclusion\nA lesion-centered immune-escape framework provides a mechanistic basis for understanding how immune dysfunction contributes to endometriosis persistence and progression. This framework may guide the development of non-hormonal immune-targeted therapies and biomarker-informed patient stratification, although substantial translational validation is still required.\nSimilar content being viewed by others\nAbbreviations\n- Akt:\n-\nProtein kinase B\n- BSA:\n-\nBovine serum albumin\n- BSA@Mif:\n-\nBovine serum albumin nanoparticles loaded with mifepristone\n- BTK:\n-\nBruton’s tyrosine kinase\n- DCs:\n-\nDendritic cells\n- CTLA-4:\n-\nCytotoxic T-lymphocyte-associated protein 4\n- ERβ:\n-\nEstrogen receptor β\n- Fe3O4 :\n-\nMagnetite (iron(II, III) oxide)\n- FOXP3:\n-\nForkhead box protein P3\n- IDO1:\n-\nIndoleamine 2,3-dioxygenase 1\n- IFN-γ:\n-\nInterferon-γ\n- IL:\n-\nInterleukin\n- mRNA:\n-\nMessenger RNA\n- M1:\n-\nClassically activated macrophage phenotype (M1-like)\n- M2:\n-\nAlternatively activated macrophage phenotype (M2-like)\n- MCs:\n-\nMast cells\n- NETs:\n-\nNeutrophil extracellular traps\n- NK:\n-\nNatural killer\n- NKG2D:\n-\nNatural killer group 2 member D\n- NPs:\n-\nNanoparticles\n- PD-1:\n-\nProgrammed cell death protein 1\n- PD-L1:\n-\nProgrammed death-ligand 1\n- PI3K:\n-\nPhosphoinositide 3-kinase\n- PLGA:\n-\nPoly(lactic-co-glycolic acid)\n- PTGIR:\n-\nProstaglandin I₂ receptor\n- siRNA:\n-\nSmall interfering RNA\n- S1P:\n-\nSphingosine-1-phosphate\n- SIRPα:\n-\nSignal regulatory protein α\n- SMAD:\n-\nSuppressor of mothers against decapentaplegic\n- SPARC:\n-\nSecreted protein acidic and rich in cysteine\n- TGF-β:\n-\nTransforming growth factor-β\n- Th:\n-\nT helper\n- TNF-α:\n-\nTumor necrosis factor-α\n- Treg:\n-\nRegulatory T cell\n- VEGF:\n-\nVascular endothelial growth factor\nAcknowledgements\nNot applicable.\nFunding\nThis work was financially supported by the National Natural Science Foundation of China (82401930, 82071616, and 82001518), Zhejiang Provincial Natural Science Foundation of China (Grant No. LQN25H270002), and the 4 + X Clinical Research Project of Women’s Hospital, School of Medicine, Zhejiang University (ZDFY2021-4 × 202).\nAuthor information\nAuthors and Affiliations\nCorresponding authors\nEthics declarations\nEthics approval and consent to participate\nNot applicable.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSupplementary Information\nRights and permissions\nOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.\nAbout this article\nCite this article\nChen, H., Zhang, M., Fei, W. et al. Immune escape in endometriosis: mechanisms, reprogramming strategies, and precision interventions. Reprod Biol Endocrinol (2026). https://doi.org/10.1186/s12958-026-01584-3\nReceived:\nAccepted:\nPublished:\nDOI: https://doi.org/10.1186/s12958-026-01584-3","source_license":"CC0","license_restricted":false}