RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cancer-derived exosomes: mediators of immune crosstalk and emerging targets for immunotherapy.
Cancer-derived exosomes: mediators of immune crosstalk and emerging targets for immunotherapy.
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外泌体是多种细胞类型分泌的纳米级细胞外囊泡,在细胞间通讯中发挥关键作用。在癌症中,肿瘤来源的外泌体——称为癌症来源外泌体(CDEs)——已成为肿瘤微环境(TME)中免疫逃逸、肿瘤进展和治疗耐药的关键调控因子。CDEs通过传递免疫抑制蛋白、细胞因子和非编码RNA来调节免疫细胞功能,最终重编程免疫监视机制。本综述深入分析了CDEs如何影响主要免疫细胞亚群——包括T细胞、B细胞、NK细胞、树突状细胞、巨噬细胞和髓源性抑制细胞——从而建立免疫抑制性TME。我们还探讨了免疫细胞来源外泌体(IDEs)作为新兴免疫治疗工具的潜力,其能够抵消CDEs的抑制效应。此外,我们重点介绍了旨在改善治疗性货物递送、肿瘤靶向和抗肿瘤免疫激活的外泌体工程策略。最后,我们讨论了外泌体谱分析如何在液体活检诊断中展现前景,以及与3D肿瘤模型和先进生物工程的整合如何加速基于外泌体的癌症免疫疗法的临床转化。
Exosomes, nanoscale extracellular vesicles secreted by various cell types, play pivotal roles in intercellular communication. In cancer, tumor-derived exosomes-referred to as cancer-derived exosomes (CDEs)-have emerged as critical regulators of immune evasion, tumor progression, and therapy resistance within the tumor microenvironment (TME).
CDEs modulate immune cell function through the transfer of immunosuppressive proteins, cytokines, and non-coding RNAs, ultimately reprogramming immune surveillance mechanisms. This review provides an in-depth analysis of how CDEs influence major immune cell subsets-including T cells, B cells, NK cells, dendritic cells, macrophages, and myeloid-derived suppressor cells-thereby establishing an immunosuppressive TME.
We also explore the potential of immune cell-derived exosomes (IDEs) as emerging immunotherapeutic tools capable of counteracting the suppressive effects of CDEs.
Furthermore, we highlight exosome engineering strategies aimed at improving therapeutic cargo delivery, tumor targeting, and antitumor immune activation.
Finally, we discuss how exosome profiling offers promise in liquid biopsy diagnostics and how integration with 3D tumor models and advanced bioengineering can accelerate the clinical translation of exosome-based cancer immunotherapies.
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