单细胞测序技术解析上皮性卵巢癌免疫微环境的研究进展

doi:10.12280/gjfckx.20240814

摘要/Abstract

摘要：

上皮性卵巢癌（epithelial ovarian cancer，EOC）是女性生殖系统恶性肿瘤中致死率最高的疾病。肿瘤免疫微环境中，免疫细胞与肿瘤细胞的相互作用可能形成恶性循环，促进肿瘤发展。因此，深入探索肿瘤免疫微环境对制定EOC的免疫治疗方案至关重要。传统高通量测序技术仅能检测细胞群体平均的基因表达水平，难以捕捉稀有异质性细胞，限制了对复杂肿瘤免疫微环境的全面理解。单细胞测序技术的出现突破了这一限制，通过高分辨率测序实现了从单细胞水平揭示肿瘤免疫微环境的异质性，这项技术能够精确识别不同免疫细胞亚群，分析其发育分化路径，并探究细胞间的相互作用。本综述还特别关注了EOC多部位的免疫微环境特征，总结了单细胞测序技术在指导个体化免疫治疗中的应用前景，并指出了未来研究方向，为促进EOC的免疫治疗提供重要参考。

关键词: 卵巢上皮癌, 肿瘤微环境, 抗肿瘤药, 免疫, 免疫疗法, 单细胞分析, 序列分析, RNA

Abstract:

Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecological malignancies. The interactions between immune cells and tumor cells in the tumor immune microenvironment may form a vicious cycle, promoting tumor development. Therefore, in-depth exploration of the tumor immune microenvironment is crucial for developing immunotherapy strategies for EOC. Traditional high-throughput sequencing techniques can only detect average gene expression levels of cell populations, masking rare heterogeneous cells and limiting our comprehensive understanding of the complex tumor immune microenvironment. The advent of single-cell sequencing technology has overcome this limitation, revealing the heterogeneity of the EOC immune microenvironment at the individual cell level through high-resolution sequencing. This technology enables precise identification of different immune cell subsets, analysis of their developmental and differentiation pathways, and investigation of intercellular interactions. This review particularly focuses on the immune microenvironment characteristics of multiple sites in EOC, summarizes the application prospects of single-cell sequencing in guiding personalized immunotherapy and developing novel treatment strategies, and points out future research directions, providing important references for advancing immunotherapy.

Key words: Carcinoma, ovarian epithelial, Tumor microenvironment, Antineoplastic agents, immunological, Immunotherapy, Single-cell analysis, Sequence analysis, RNA

李丹宁, 汪希鹏. 单细胞测序技术解析上皮性卵巢癌免疫微环境的研究进展[J]. 国际妇产科学杂志, 2024, 51(6): 654-658.

LI Dan-ning, WANG Xi-peng. Research Progress on Utilizing Single-Cell Sequencing Technology to Investigate Tumor Immune Microenvironment in Epithelial Ovarian Cancer[J]. Journal of International Obstetrics and Gynecology, 2024, 51(6): 654-658.

参考文献 23

[1]	郑荣寿, 张思维, 孙可欣, 等. 2016年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2023, 45(3):212-220. doi: 10.3760/cma.j.cn112152-20220922-00647.
[2]	Tang F, Barbacioru C, Wang Y, et al. mRNA-Seq whole-transcriptome analysis of a single cell[J]. Nat Methods, 2009, 6(5):377-382. doi: 10.1038/nmeth.1315. pmid: 19349980
[3]	Sun F, Li H, Sun D, et al. Single-cell omics: experimental workflow, data analyses and applications[J]. Sci China Life Sci, 2024 Jul 23. doi: 10.1007/s11427-023-2561-0.
[4]	Buenrostro JD, Wu B, Chang HY, et al. ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide[J]. Curr Protoc Mol Biol, 2015, 109:21.29.1-21.29.9. doi: 10.1002/0471142727.mb2129s109.
[5]	Paijens ST, Vledder A, de Bruyn M, et al. Tumor-infiltrating lymphocytes in the immunotherapy era[J]. Cell Mol Immunol, 2021, 18(4):842-859. doi: 10.1038/s41423-020-00565-9. pmid: 33139907
[6]	Reina-Campos M, Scharping NE, Goldrath AW. CD8⁺ T cell metabolism in infection and cancer[J]. Nat Rev Immunol, 2021, 21(11):718-738. doi: 10.1038/s41577-021-00537-8. pmid: 33981085
[7]	Wing JB, Tanaka A, Sakaguchi S. Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer[J]. Immunity, 2019, 50(2):302-316. doi: 10.1016/j.immuni.2019.01.020.
[8]	Shang B, Liu Y, Jiang SJ, et al. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis[J]. Sci Rep, 2015, 5:15179. doi: 10.1038/srep15179. pmid: 26462617
[9]	Gao Y, Chen L, Cai G, et al. Heterogeneity of immune microenvironment in ovarian cancer and its clinical significance: a retrospective study[J]. Oncoimmunology, 2020, 9(1):1760067. doi: 10.1080/2162402X.2020.1760067.
[10]	Cho U, Kim B, Kim S, et al. Pro-inflammatory M1 macrophage enhances metastatic potential of ovarian cancer cells through NF-κB activation[J]. Mol Carcinog, 2018, 57(2):235-242. doi: 10.1002/mc.22750.
[11]	Launonen IM, Lyytikäinen N, Casado J, et al. Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer[J]. Nat Commun, 2022, 13(1):835. doi: 10.1038/s41467-022-28389-3. pmid: 35149709
[12]	Zheng X, Wang X, Cheng X, et al. Single-cell analyses implicate ascites in remodeling the ecosystems of primary and metastatic tumors in ovarian cancer[J]. Nat Cancer, 2023, 4(8):1138-1156. doi: 10.1038/s43018-023-00599-8.
[13]	Luo Y, Xia Y, Liu D, et al. Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors[J]. Cell, 2024, 187(18):4905-4925. e24. doi: 10.1016/j.cell.2024.06.013.
[14]	Chai C, Liang L, Mikkelsen NS, et al. Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer[J]. Commun Biol, 2024, 7(1):131. doi: 10.1038/s42003-024-05826-1. pmid: 38278958
[15]	Liu B, Hu X, Feng K, et al. Temporal single-cell tracing reveals clonal revival and expansion of precursor exhausted T cells during anti-PD-1 therapy in lung cancer[J]. Nat Cancer, 2022, 3(1):108-121. doi: 10.1038/s43018-021-00292-8.
[16]	Hornburg M, Desbois M, Lu S, et al. Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer[J]. Cancer Cell, 2021, 39(7):928-944. e6. doi: 10.1016/j.ccell.2021.04.004. pmid: 33961783
[17]	Tang F, Li J, Qi L, et al. A pan-cancer single-cell panorama of human natural killer cells[J]. Cell, 2023, 186(19):4235-4251.e20. doi: 10.1016/j.cell.2023.07.034.
[18]	Yang Y, Chen X, Pan J, et al. Pan-cancer single-cell dissection reveals phenotypically distinct B cell subtypes[J]. Cell, 2024, 187(17):4790-4811.e22. doi: 10.1016/j.cell.2024.06.038.
[19]	Zhang AW, McPherson A, Milne K, et al. Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer[J]. Cell, 2018, 173(7):1755-1769.e22. doi: 10.1016/j.cell.2018.03.073. pmid: 29754820
[20]	Zheng C, Zheng L, Yoo JK, et al. Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing[J]. Cell, 2017, 169(7):1342-1356.e16. doi: 10.1016/j.cell.2017.05.035. pmid: 28622514
[21]	Powles T, Csöszi T, Özgüroğlu M, et al. Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2021, 22(7):931-945. doi: 10.1016/S1470-2045(21)00152-2. pmid: 34051178
[22]	Chen Y, Wang D, Li Y, et al. Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer[J]. Cancer Cell, 2024, 42(7):1268-1285.e7. doi: 10.1016/j.ccell.2024.06.009. pmid: 38981439
[23]	Guo X, Zhang Y, Zheng L, et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing[J]. Nat Med, 2018, 24(7):978-985. doi: 10.1038/s41591-018-0045-3. pmid: 29942094