CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Extracellular Vesicles & Co.: scaring immune cells in the TME since ever.
Extracellular Vesicles & Co.: scaring immune cells in the TME since ever.
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实体瘤周围的健康组织,即肿瘤微环境(TME),是一个极其复杂的由细胞、细胞外基质和各种性质的信号组成的体系,它们支持和保护癌细胞的生长。癌细胞与TME之间发生的相互作用不仅对肿瘤生长、侵袭和转移至关重要,而且在调节免疫系统对癌症的应答中也发挥关键作用,反之亦然。事实上,肿瘤浸润免疫细胞(如T淋巴细胞和NK 细胞)的活性在很大程度上受到它们在TME中接收到的信号(主要是配体/受体和旁分泌信号)的影响,这些信号常常产生免疫抑制性环境。近年来,越来越明显的是,可溶性和受体信号传导并非TME中细胞间通讯的唯一方式,细胞外囊泡(如外泌体)发挥着核心作用。在最近发现的几种新型囊泡中,迁移体似乎引起了极大的关注,因为它们不仅与其他囊泡不同,而且据报道能够传递高度异质性的信息,能够深刻影响受体细胞的行为。事实上,不同类别的细胞外囊泡所发挥的作用,尤其是在TME中,依赖于它们从来源细胞的无方向性扩散,而迁移细胞释放的迁移体则具有方向性效应。迁移体的生物学及其在癌症进展、播散和治疗耐药中的参与仍然是一个很大程度上未知的领域,但预计在未来会有前景广阔的发展。
The health tissue surrounding a solid tumor, namely the tumor microenvironment (TME), is an extremely complex universe of cells, extracellular matrix, and signals of various nature, that support and protect the growth of cancer cells. The interactions taking place between cancer cells and the TME are crucial not only for tumor growth, invasion, and metastasis but they also play a key role in modulating immune system responses to cancer, and vice-versa. Indeed, tumor-infiltrating immune cells (e. g. , T lymphocytes and natural killers) activity is greatly affected by signals (mostly ligands/receptors and paracrine) they receive in the TME, which frequently generate an immunosuppressive milieu. In the last years, it has become evident that soluble and receptor signaling is not the only way of communication between cells in the TME, with extracellular vesicles, such as exosomes, playing a central role.
Among the different new kind of vesicles recently discovered, migrasomes look like to be of extreme interest as they are not only different from the others, but also have been reported as able to deliver a very heterogeneous kind of messages, able to profoundly affect recipient cells' behavior.
Indeed, the role played by the different classes of extracellular vesicles, especially in the TME, relies on their not-directional diffusion from the originating cells, while migrasomes released from migrating cells do have a directional effect. Migrasomes biology and their involvement in cancer progression, dissemination, and resistance to therapy is still a largely obscure field, but with promising development foreseen in the next future.
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