TCR组库测序在子宫内膜异位症研究中的前景与挑战
Prospects and Challenges of TCR Repertoire Sequencing in Endometriosis Research
DOI: 10.12677/acm.2026.163893, PDF,    科研立项经费支持
作者: 容红红, 杨宇欣, 凌子怡, 赖洁钰：暨南大学第一临床医学院，广东 广州；李 平：暨南大学基础医学与公共卫生学院，广东 广州；帅翰林*：暨南大学附属第一医院妇科，广东 广州
关键词: 子宫内膜异位症；TCR组库测序；免疫微环境；免疫治疗；Endometriosis； TCR Repertoire Sequencing； Immune Microenvironment； Immunotherapy
摘要: 子宫内膜异位症(Endometriosis, EMs)是一种以育龄期女性盆腔疼痛与不孕为主要临床表现的慢性炎症性疾病，其病理机制尚未完全阐明。目前大多数研究聚焦于免疫细胞亚群比例及炎症因子表达水平的改变，而对于驱动疾病发生发展的抗原特异性T细胞应答机制，仍缺乏深入且系统的探究。T细胞受体(TCR)组库测序是近年来兴起的一项分子检测技术，可全面解析个体T细胞的克隆多样性、谱系组成及动态变化规律，能精准捕捉抗原特异性T细胞的应答特征。本文系统阐述EMs的T细胞免疫学特征，介绍TCR测序技术原理及其在相关疾病中的应用，进而论证该技术应用于EMs的研究价值以及可能面临的技术挑战，以期为揭示EMs的抗原特异性免疫病理机制和探索新型免疫干预策略提供新的视角和工具。
Abstract: Endometriosis (EMs) is a chronic inflammatory disease that primarily manifests as pelvic pain and infertility in women of childbearing age and its pathological mechanism has not been fully elucidated. At present, most studies have focused on changes in the proportion of immune cell subsets and the expression levels of inflammatory factors, whereas in-depth and systematic investigations into the antigen-specific T cell response mechanisms that drive the occurrence and development of the disease are still lacking. T cell receptor (TCR) repertoire sequencing is an emerging molecular detection technology in recent years, which can comprehensively analyze the clonal diversity, lineage composition and dynamic variation rules of individual T cells, and accurately capture the response characteristics of antigen-specific T cells. This paper systematically elaborates on the T cell immunological characteristics of EMs, introduces the technical principles of TCR sequencing and its applications in related diseases, and further demonstrates the feasibility of applying this technology to EMs research as well as the potential technical challenges and future directions, aiming to provide new perspectives and tools for revealing the antigen-specific immunopathological mechanisms of EMs and exploring novel immune intervention strategies.
文章引用：容红红, 杨宇欣, 凌子怡, 赖洁钰, 李平, 帅翰林. TCR组库测序在子宫内膜异位症研究中的前景与挑战[J]. 临床医学进展, 2026, 16(3): 1169-1175. https://doi.org/10.12677/acm.2026.163893

参考文献

[1] Fan, D., Wang, X., Shi, Z., Jiang, Y., Zheng, B., Xu, L., et al. (2023) Understanding Endometriosis from an Immunomicroenvironmental Perspective. Chinese Medical Journal, 136, 1897-1909. [Google Scholar] [CrossRef] [PubMed]
[2] Kiesel, L. and Sourouni, M. (2019) Diagnosis of Endometriosis in the 21st Century. Climacteric, 22, 296-302. [Google Scholar] [CrossRef] [PubMed]
[3] Symons, L.K., Miller, J.E., Kay, V.R., Marks, R.M., Liblik, K., Koti, M., et al. (2018) The Immunopathophysiology of Endometriosis. Trends in Molecular Medicine, 24, 748-762. [Google Scholar] [CrossRef] [PubMed]
[4] Vallvé-Juanico, J., Houshdaran, S. and Giudice, L.C. (2019) The Endometrial Immune Environment of Women with Endometriosis. Human Reproduction Update, 25, 565-592. [Google Scholar] [CrossRef] [PubMed]
[5] Rosati, E., Dowds, C.M., Liaskou, E., Henriksen, E.K.K., Karlsen, T.H. and Franke, A. (2017) Overview of Methodologies for T-Cell Receptor Repertoire Analysis. BMC Biotechnology, 17, Article No. 61. [Google Scholar] [CrossRef] [PubMed]
[6] Glanville, J., Huang, H., Nau, A., Hatton, O., Wagar, L.E., Rubelt, F., et al. (2017) Identifying Specificity Groups in the T Cell Receptor Repertoire. Nature, 547, 94-98. [Google Scholar] [CrossRef] [PubMed]
[7] Abramiuk, M., Grywalska, E., Małkowska, P., Sierawska, O., Hrynkiewicz, R. and Niedźwiedzka-Rystwej, P. (2022) The Role of the Immune System in the Development of Endometriosis. Cells, 11, Article 2028. [Google Scholar] [CrossRef] [PubMed]
[8] Kedzierska, A.E., Lorek, D., Slawek, A., Karmowski, M., Kalota, A., Pajak, J., et al. (2025) IL-24 Producing Regulatory T and B Lymphocytes in Endometriosis. Frontiers in Immunology, 16, Article 1582762. [Google Scholar] [CrossRef] [PubMed]
[9] Riccio, L.d.G.C., Santulli, P., Marcellin, L., Abrão, M.S., Batteux, F. and Chapron, C. (2018) Immunology of Endometriosis. Best Practice & Research Clinical Obstetrics & Gynaecology, 50, 39-49. [Google Scholar] [CrossRef] [PubMed]
[10] Szukiewicz, D. (2022) Epigenetic Regulation and T-Cell Responses in Endometriosis—Something Other than Autoimmunity. Frontiers in Immunology, 13, Article 943839. [Google Scholar] [CrossRef] [PubMed]
[11] Knez, J., Kovačič, B. and Goropevšek, A. (2024) The Role of Regulatory T-Cells in the Development of Endometriosis. Human Reproduction, 39, 1367-1380. [Google Scholar] [CrossRef] [PubMed]
[12] Yao, B., Zheng, R., Yang, Y., Zhao, Z., Lash, G.E., Guo, B., et al. (2025) Therapeutic Targeting of Interleukin-17c Signaling in Carcinogenesis of Endometriosis. Cell Reports Medicine, 6, Article ID: 102464. [Google Scholar] [CrossRef] 
[13] Kisovar, A., Becker, C.M., Granne, I. and Southcombe, J.H. (2023) The Role of CD8+ T Cells in Endometriosis: A Systematic Review. Frontiers in Immunology, 14, Article 1225639. [Google Scholar] [CrossRef] [PubMed]
[14] Yu, H., Huang, J., Liu, Y., Chen, H., Li, Y., Lin, J., et al. (2024) TIM-3 Expression in Endometriosis and Its Correlation with Disease Severity. Journal of Reproductive Immunology, 164, Article ID: 104267.
[15] Dudley, D.D., Sekiguchi, J., Zhu, C., Sadofsky, M.J., Whitlow, S., DeVido, J., et al. (2003) Impaired V(D)J Recombination and Lymphocyte Development in Core RAG1-Expressing Mice. The Journal of Experimental Medicine, 198, 1439-1450. [Google Scholar] [CrossRef] [PubMed]
[16] Turner, S.J., Doherty, P.C., McCluskey, J. and Rossjohn, J. (2006) Structural Determinants of T-Cell Receptor Bias in Immunity. Nature Reviews Immunology, 6, 883-894. [Google Scholar] [CrossRef] [PubMed]
[17] 方智浩, 龚方戚. TCR组库分析及应用的最新进展[J]. 中国免疫学杂志, 2025, 41(8): 2012-2018.
[18] Dupic, T., Marcou, Q., Walczak, A.M. and Mora, T. (2019) Genesis of the αβ T-Cell Receptor. PLOS Computational Biology, 15, e1006874. [Google Scholar] [CrossRef] [PubMed]
[19] Zheng, G.X.Y., Terry, J.M., Belgrader, P., Ryvkin, P., Bent, Z.W., Wilson, R., et al. (2017) High-Throughput and Single-Cell T Cell Receptor Sequencing Technologies. Nature Methods, 14, 865-871.
[20] Mora, T. and Walczak, A.M. (2016) Quantifying Lymphocyte Receptor Diversity. arXiv: 1604.00487.
[21] Woodsworth, D.J., Castellarin, M. and Holt, R.A. (2013) Sequence Analysis of T-Cell Repertoires in Health and Disease. Genome Medicine, 5, Article No. 98. [Google Scholar] [CrossRef] [PubMed]
[22] Joshi, K., Milighetti, M. and Chain, B.M. (2022) Application of T Cell Receptor (TCR) Repertoire Analysis for the Advancement of Cancer Immunotherapy. Current Opinion in Immunology, 74, 1-8. [Google Scholar] [CrossRef] [PubMed]
[23] Zhu, S., Zhang, C., Cao, D., Bai, J., Yu, S., Chen, J., et al. (2022) Genomic and TCR Profiling Data Reveal the Distinct Molecular Traits in Epithelial Ovarian Cancer Histotypes. Oncogene, 41, 3093-3103. [Google Scholar] [CrossRef] [PubMed]
[24] Yu, X., Ye, J., Hathaway, C.A., Liao, J., Liu, P., et al. (2024) Quantifiable TCR Repertoire Changes in Pre-Diagnostic Blood Specimens among High-Grade Ovarian Cancer Patients. Journal of Clinical Oncology, 42, Article ID: 10507.
[25] Kim, T., Lim, H., Jun, S., Park, J., Lee, D., Lee, J.H., et al. (2023) Globally Shared TCR Repertoires within the Tumor-Infiltrating Lymphocytes of Patients with Metastatic Gynecologic Cancer. Scientific Reports, 13, Article No. 20485. [Google Scholar] [CrossRef] [PubMed]
[26] Guo, J., Luo, N., Ai, G., Yang, W., Zhu, J., Li, C., et al. (2022) Eradicating Tumor in a Recurrent Cervical Cancer Patient with Autologous Tumor-Infiltrating Lymphocytes and a Modified Lymphodepleting Regimen. Journal for ImmunoTherapy of Cancer, 10, e003887. [Google Scholar] [CrossRef] [PubMed]
[27] Cui, J., Lin, K., Yuan, S., Jin, Y., Chen, X., Su, X., et al. (2018) TCR Repertoire as a Novel Indicator for Immune Monitoring and Prognosis Assessment of Patients with Cervical Cancer. Frontiers in Immunology, 9, Article 2729. [Google Scholar] [CrossRef] [PubMed]
[28] Miller, D., Romero, R., Myers, L., Xu, Y., Arenas-Hernandez, M., Galaz, J., et al. (2023) Immunosequencing and Profiling of T Cells at the Maternal-Fetal Interface of Women with Preterm Labor and Chronic Chorioamnionitis. The Journal of Immunology, 211, 1082-1098. [Google Scholar] [CrossRef] [PubMed]
[29] Guo, C., Cai, R., Cao, X., Yang, Y., Wang, Q., He, R., et al. (2019) Deep Targeted Sequencing Reveals the Diversity of TRB-CDR3 Repertoire in Patients with Preeclampsia. Human Immunology, 80, 848-854. [Google Scholar] [CrossRef] [PubMed]
[30] Jiang, X., Wang, S., Zhou, C., Wu, J., Jiao, Y., Lin, L., et al. (2020) Comprehensive TCR Repertoire Analysis of CD4+ T-Cell Subsets in Rheumatoid Arthritis. Journal of Autoimmunity, 109, Article ID: 102432. [Google Scholar] [CrossRef] [PubMed]
[31] Chen, Y., Zhang, Y., Lin, C., Li, Z., Huang, H., Chen, Y., et al. (2020) Characterisation of T and B Cell Receptor Repertoire in Patients with Systemic Lupus Erythematosus. Clinical and Experimental Rheumatology, 38, 450-458.
[32] Sui, W., Hou, X., Zou, G., Che, W., Yang, M., Zheng, C., et al. (2015) Composition and Variation Analysis of the TCR β-Chain CDR3 Repertoire in Systemic Lupus Erythematosus Using High-Throughput Sequencing. Molecular Immunology, 67, 455-464. [Google Scholar] [CrossRef] [PubMed]
[33] Shao, L., Liu, Y., Mei, J., Li, D., Chen, L., Pan, Q., et al. (2020) High-Throughput Sequencing Reveals the Diversity of TCR β Chain CDR3 Repertoire in Patients with Severe Acne. Molecular Immunology, 120, 23-31. [Google Scholar] [CrossRef] [PubMed]
[34] Fang, Y., Shen, B., Dai, Q., Xie, Q., Li, X., Wu, W., et al. (2023) Composition and Diversity Analysis of the TCR CDR3 Repertoire in Patients with Idiopathic Orbital Inflammation Using High-Throughput Sequencing. BMC Ophthalmology, 23, Article No. 491. [Google Scholar] [CrossRef] [PubMed]
[35] Klemmt, P.A.B. and Starzinski-Powitz, A. (2018) Molecular and Cellular Pathogenesis of Endometriosis. Current Women’s Health Reviews, 14, 106-116. [Google Scholar] [CrossRef] [PubMed]
[36] Pogorelyy, M.V., Minervina, A.A., Chudakov, D.M., Mamedov, I.Z., Lebedev, Y.B., Mora, T., et al. (2018) Method for Identification of Condition-Associated Public Antigen Receptor Sequences. eLife, 7, e33050. [Google Scholar] [CrossRef] [PubMed]

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