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肿瘤来源的细胞外囊泡在 NK 细胞免疫逃逸中的作用:分子机制与治疗启示

英文原题:Cancer-derived extracellular vesicles in natural killer cell immune evasion: Molecular mechanisms and therapeutic insights.

PubMed 2025/05/31(内容时间) Mol Ther Q1 · IF 11.4(JCR 2025)

研究概要

NK 细胞是先天淋巴细胞,具备快速识别和消灭癌细胞的能力。

中文摘要

NK 细胞是先天淋巴细胞,具备快速识别和清除癌细胞的能力。然而,癌细胞会释放纳米级细胞外囊泡,这些囊泡可诱导免疫抑制性肿瘤微环境,进而阻碍NK 细胞的免疫监视。研究报道,来自不同癌症(如急性髓系白血病、黑色素瘤、间皮瘤、头颈部鳞状细胞癌、肺癌、乳腺癌、肝细胞癌和胰腺导管腺癌)的细胞外囊泡可通过抑制细胞溶解蛋白和下调参与识别致癌细胞的受体表达,诱导NK 细胞功能障碍。此外,癌症来源的细胞外囊泡还可干扰NK 细胞的存活、增殖、细胞迁移和代谢功能。因此,细胞外囊泡诱导的NK 细胞抑制已成为研究和开发新治疗策略的关键靶点,旨在恢复和增强这些免疫细胞的杀肿瘤潜力。在此,我们总结了目前关于癌症来源细胞外囊泡与NK 细胞相互作用、其在免疫抑制中的作用、对开发高效细胞免疫治疗的意义以及该领域尚待解决的问题。

展开英文摘要原文

Natural killer cells are innate lymphocytes equipped with the ability to rapidly identify and eliminate cancer cells. However, cancer cells release nanosized extracellular vesicles that can induce an immunosuppressive tumor microenvironment, subsequently hindering natural killer cell immunosurveillance. Studies have reported that extracellular vesicles derived from different cancers, such as acute myeloid leukemia, melanoma, mesothelioma, head and neck squamous carcinoma, lung carcinoma, breast cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, can induce natural killer cell dysfunction by suppressing cytolytic proteins and downregulating expression of receptors involved in the recognition of oncogenic cells. Additionally, cancer-derived extracellular vesicles can interfere with natural killer cell survival, proliferation, cell migration, and metabolic functions. Therefore, extracellular vesicle-induced natural killer cell suppression has emerged as a key target for research and new therapeutic approaches to recover and enhance the tumoricidal potential of these immune cells. Here, we summarize the current knowledge regarding cancer-derived extracellular vesicles and natural killer cell interactions, their role in immunosuppression, implications for developing efficient cellular immunotherapies and outstanding questions in this field.

论文信息

作者
Coleborn E、Ghebosu R、Wolfram J、Souza-Fonseca-Guimaraes F
第一作者单位
Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4102, Australia.Australia
通讯作者单位
Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4102, Australia. Electronic address: f.guimaraes@uq.edu.au.Australia
文献类型
综述
期刊
Molecular therapy : the journal of the American Society of Gene Therapy2025 Sep 3
原文标识
PubMed 40452185 · DOI 10.1016/j.ymthe.2025.05.038