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宫颈癌免疫微环境的靶向治疗:当前研究与进展

Targeting immune microenvironment in cervical cancer: current research and advances.

作者信息

Zhang Zhen, Liu Miao, An Yu, Gao Chongqing, Wang Tao, Zhang Zhi, Zhang Guixiang, Li Shuo, Li Wei, Li Mengjia, Wang Gangcheng

机构信息

Department of Abdominal and Pelvic Tumor Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.

出版信息

J Transl Med. 2025 Aug 8;23(1):888. doi: 10.1186/s12967-025-06896-3.

DOI:10.1186/s12967-025-06896-3
PMID:40781691
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12335084/
Abstract

The immune microenvironment plays a critical role in pathogenesis and treatment response of cervical cancer. This review comprehensively examines the cellular and molecular components of the tumor immune microenvironment (TIME) in cervical cancer, encompassing patterns of immune cell infiltration (T cells, B cells, NK cells, DCs, TAMs), immune checkpoint molecules, and cytokine/chemokine networks. We emphasize recent advances in understanding TIME heterogeneity, enabled by high-resolution spatial mapping and single-cell sequencing technologies, focusing specifically on differences across disease stages and treatment approaches. The review systematically evaluates immunotherapeutic strategies, such as immune checkpoint inhibitors, adoptive cell therapies, and therapeutic vaccines, discussing their mechanisms of action, clinical efficacy, and challenges. By synthesizing insights from both preclinical and clinical studies, our aim is to offer a translational perspective on targeting the TIME to enhance outcomes for cervical cancer patients.

摘要

免疫微环境在宫颈癌的发病机制和治疗反应中起着关键作用。本综述全面研究了宫颈癌肿瘤免疫微环境(TIME)的细胞和分子成分,包括免疫细胞浸润模式(T细胞、B细胞、NK细胞、树突状细胞、肿瘤相关巨噬细胞)、免疫检查点分子以及细胞因子/趋化因子网络。我们强调了通过高分辨率空间映射和单细胞测序技术在理解TIME异质性方面取得的最新进展,特别关注不同疾病阶段和治疗方法之间的差异。该综述系统评估了免疫治疗策略,如免疫检查点抑制剂、过继性细胞疗法和治疗性疫苗,讨论了它们的作用机制、临床疗效和挑战。通过综合临床前和临床研究的见解,我们的目标是提供一个关于靶向TIME以改善宫颈癌患者预后的转化视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d81/12335084/50796c233eff/12967_2025_6896_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d81/12335084/a1f3849c90c3/12967_2025_6896_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d81/12335084/50796c233eff/12967_2025_6896_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d81/12335084/a1f3849c90c3/12967_2025_6896_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d81/12335084/50796c233eff/12967_2025_6896_Fig2_HTML.jpg

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本文引用的文献

1
Chemoradiotherapy-induced ACKR2 tumor cells drive CD8 T cell senescence and cervical cancer recurrence.放化疗诱导的 ACKR2 肿瘤细胞驱动 CD8 T 细胞衰老和宫颈癌复发。
Cell Rep Med. 2024 May 21;5(5):101550. doi: 10.1016/j.xcrm.2024.101550. Epub 2024 May 8.
2
Hepatocytes coordinate immune evasion in cancer via release of serum amyloid A proteins.肝细胞通过释放血清淀粉样蛋白A来协调癌症中的免疫逃逸。
Nat Immunol. 2024 May;25(5):755-763. doi: 10.1038/s41590-024-01820-1. Epub 2024 Apr 19.
3
Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1-2, open-label, multicohort trial.
纳武利尤单抗联合或不联合伊匹木单抗治疗复发性或转移性宫颈癌患者(CheckMate 358):一项1/2期、开放标签、多队列试验
Lancet Oncol. 2024 May;25(5):588-602. doi: 10.1016/S1470-2045(24)00088-3. Epub 2024 Apr 9.
4
Oct4 activates IL-17A to orchestrate M2 macrophage polarization and cervical cancer metastasis.Oct4 激活 IL-17A 以协调 M2 巨噬细胞极化和宫颈癌转移。
Cancer Immunol Immunother. 2024 Mar 2;73(4):73. doi: 10.1007/s00262-023-03596-z.
5
Pterostilbene upregulates MICA/B via the PI3K/AKT signaling pathway to enhance the capability of natural killer cells to kill cervical cancer cells.紫檀芪通过 PI3K/AKT 信号通路上调 MICA/B,从而增强自然杀伤细胞杀伤宫颈癌的能力。
Exp Cell Res. 2024 Feb 15;435(2):113933. doi: 10.1016/j.yexcr.2024.113933. Epub 2024 Feb 1.
6
Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer.多组学分析揭示了 γδ T 淋巴细胞改善宫颈癌肿瘤微环境、免疫治疗疗效和预后的作用。
J Immunother Cancer. 2024 Jan 9;12(1):e008355. doi: 10.1136/jitc-2023-008355.
7
Anti-CTLA-4 nanobody as a promising approach in cancer immunotherapy.抗 CTLA-4 纳米抗体作为癌症免疫治疗的一种有前途的方法。
Cell Death Dis. 2024 Jan 8;15(1):17. doi: 10.1038/s41419-023-06391-x.
8
Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial.阿替利珠单抗联合贝伐珠单抗和化疗治疗转移性、持续性或复发性宫颈癌(BEATcc):一项随机、开放标签、3 期临床试验。
Lancet. 2024 Jan 6;403(10421):31-43. doi: 10.1016/S0140-6736(23)02405-4. Epub 2023 Dec 1.
9
Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance.宫颈鳞状细胞癌的多组学分析确定了具有生物学和临床相关性的细胞生态系统。
Nat Genet. 2023 Dec;55(12):2175-2188. doi: 10.1038/s41588-023-01570-0. Epub 2023 Nov 20.
10
Interactions of Indoleamine 2,3-dioxygenase-expressing LAMP3 dendritic cells with CD4 regulatory T cells and CD8 exhausted T cells: synergistically remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications.吲哚胺 2,3-双加氧酶表达的 LAMP3 树突状细胞与 CD4 调节性 T 细胞和 CD8 耗竭性 T 细胞的相互作用:协同重塑宫颈癌的免疫抑制微环境及其治疗意义。
Cancer Commun (Lond). 2023 Nov;43(11):1207-1228. doi: 10.1002/cac2.12486. Epub 2023 Oct 4.