文章：

肿瘤来源的细胞外囊泡与免疫受体细胞之间的串扰及癌症转移

Crosstalk of Tumor-Derived Extracellular Vesicles with Immune Recipient Cells and Cancer Metastasis

原文发布日期：7 January 2026

DOI: 10.3390/cancers18020196

类型: Article

开放获取: 是

英文摘要：

Background. Contributions of tumor-derived extracellular vesicles, TEX, to tumor progression and metastasis involve their crosstalk with immune cells in the tumor microenvironment. This crosstalk results in metabolic reprogramming of immune cells from anti-tumor to pro-tumor activity. Mechanistic underpinnings of the TEX entry and delivery of molecular signals responsible for metabolic reprogramming may be unique for different types of immune cells.Methods. An in vitro model of THP-1 myeloid cells co-incubated with TEX illustrates the role TEX play in polarization of macrophages to TAMs.Results. In THP-1 cells, the dominant signaling pathway of melanoma cell-derived TEX involves HSP-90/TLR2. This leads to activation of the NF-κB and MAP kinase pathways and initiates THP-1 cell polarization from M0 to M2 with strong expression of immunosuppressive PD-L1. TEX may be seen as “danger” by the myeloid cells, which utilize the pattern recognition receptors (PRR), such as PAMPs or DAMPs, for engaging the complementary ligands carried by TEX. The same melanoma TEX signaling to T cells via DAMPs induced mitochondrial stress, resulting in T-cell apoptosis.Conclusions. As the signaling receptors/ligands in TEX are determined by the tumor, it appears that the tumor equips TEX with an address recognizing specific PRRs expressed on different recipient immune cells. Thus, TEX, acting like pathogens, are equipped by the tumor to alter the context of intercellular crosstalk and impose a distinct autophagy-not-apoptosis signature in recipient THP-1 cells. The tumor might endorse TEX to promote tumor progression and metastasis by enabling them to engage the signaling system normally used by immune cells for defense against pathogens.

摘要翻译： 

背景：肿瘤源性细胞外囊泡（TEX）对肿瘤进展和转移的促进作用，涉及其与肿瘤微环境中免疫细胞的相互作用。这种相互作用导致免疫细胞发生从抗肿瘤活性向促肿瘤活性的代谢重编程。TEX进入不同免疫细胞并传递代谢重编程信号的分子机制可能具有细胞类型特异性。

方法：通过THP-1髓系细胞与TEX共培养的体外模型，阐明TEX在巨噬细胞向肿瘤相关巨噬细胞（TAMs）极化中的作用。

结果：在THP-1细胞中，黑色素瘤来源TEX主要通过HSP-90/TLR2信号通路发挥作用。该通路激活NF-κB和MAP激酶途径，启动THP-1细胞从M0型向M2型极化，并高表达免疫抑制分子PD-L1。髓系细胞可能将TEX识别为“危险信号”，通过模式识别受体（PRR，如PAMPs或DAMPs）与TEX携带的互补配体结合。同一黑色素瘤TEX通过DAMPs向T细胞传递信号时，会诱导线粒体应激，导致T细胞凋亡。

结论：由于TEX的信号受体/配体由肿瘤决定，肿瘤似乎为TEX配备了能够识别不同受体免疫细胞表面特定PRR的“地址识别系统”。因此，TEX如同病原体般被肿瘤武装，用于改变细胞间相互作用的模式，并在受体THP-1细胞中形成独特的“自噬非凋亡”特征。肿瘤可能通过授权TEX利用免疫细胞抵御病原体的信号系统，来促进肿瘤进展和转移。

原文链接：

Crosstalk of Tumor-Derived Extracellular Vesicles with Immune Recipient Cells and Cancer Metastasis