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:The roles of small extracellular vesicles in cancer and immune regulation and translational potential in cancer therapy.
The roles of small extracellular vesicles in cancer and immune regulation and translational potential in cancer therapy.
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细胞外囊泡(EVs)促进蛋白质、脂质和核酸的细胞外转移,并介导肿瘤环境中多种细胞间的细胞间通讯。小细胞外囊泡(sEVs)被定义为直径约50至150 nm的EVs。肿瘤来源的sEVs(TDsEVs)和免疫细胞来源的sEVs具有显著的免疫活性,并参与癌症进展和免疫应答。已在TDsEVs上鉴定出癌症特异性分子,可作为癌症诊断和预后的生物标志物,以及基于TDsEVs疫苗的变应原。多种单核细胞,包括但不限于树突状细胞(DCs)、B细胞、T细胞、自然杀伤(NK)细胞、巨噬细胞和髓源性抑制细胞(MDSCs),分泌sEVs,在复杂的免疫网络中调节免疫应答,具有促肿瘤或抗肿瘤作用。经过工程化修饰后,来自免疫细胞和其他供体细胞的sEVs可提供改善的靶向性和生物学效应。结合其天然特性,这些工程化sEVs作为药物载体具有巨大潜力。当用于多种癌症治疗时,它们可辅助增强多种治疗药物的安全性和抗肿瘤疗效。
总之,肿瘤环境中的天然sEVs和携带效应物货物的工程化sEVs均被认为在癌症诊断和治疗中展现出有前景的潜力。
Extracellular vesicles (EVs) facilitate the extracellular transfer of proteins, lipids, and nucleic acids and mediate intercellular communication among multiple cells in the tumour environment. Small extracellular vesicles (sEVs) are defined as EVs range in diameter from approximately 50 to 150 nm. Tumour-derived sEVs (TDsEVs) and immune cell-derived sEVs have significant immunological activities and participate in cancer progression and immune responses. Cancer-specific molecules have been identified on TDsEVs and can function as biomarkers for cancer diagnosis and prognosis, as well as allergens for TDsEVs-based vaccination.
Various monocytes, including but not limited to dendritic cells (DCs), B cells, T cells, natural killer (NK) cells, macrophages, and myeloid-derived suppressor cells (MDSCs), secrete sEVs that regulate immune responses in the complex immune network with either protumour or antitumour effects. After engineered modification, sEVs from immune cells and other donor cells can provide improved targeting and biological effects.
Combined with their naïve characteristics, these engineered sEVs hold great potential as drug carriers. When used in a variety of cancer therapies, they can adjunctly enhance the safety and antitumor efficacy of multiple therapeutics. In summary, both naïve sEVs in the tumour environment and engineered sEVs with effector cargoes are regarded as showing promising potential for use in cancer diagnostics and therapeutics.
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