肿瘤来源的小细胞外囊泡通过重塑全身免疫宏观环境促进肿瘤进展。
Tumour-derived small extracellular vesicles contribute to the tumour progression through reshaping the systemic immune macroenvironment.
机构信息
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 510095, Guangzhou, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, 511436, Guangzhou, China.
出版信息
Br J Cancer. 2023 Mar;128(7):1249-1266. doi: 10.1038/s41416-023-02175-4. Epub 2023 Feb 8.
BACKGROUND
Tumour-derived small extracellular vesicles (sEVs) play a crucial role in cancer immunomodulation. In addition to tumour immune microenvironment, the peripheral immune system also contributes significantly to cancer progression and is essential for anticancer immunity. However, a comprehensive definition of which and how peripheral immune lineages are regulated by tumour-derived sEVs during cancer development remains incomplete.
METHODS
In this study, we used mass cytometry with extensive antibody panels to comprehensively construct the systemic immune landscape in response to tumour development and tumour-derived sEVs.
RESULTS
Systemic immunity was dramatically altered by tumour growth and tumour-derived sEVs. Tumour-derived sEVs significantly and extensively affected immune cell population composition as well as intracellular pathways, resulting in an immunosuppressive peripheral and tumour immune microenvironment, characterised by increased myeloid-derived suppressor cells and decreased Ly6CCD8 T cells. These sEVs largely promoted hematopoietic recovery and accelerate the differentiation towards myeloid-derived suppressor cells. The knockdown of Rab27a reduced sEV secretion from tumour cells and delayed tumour growth and metastasis in vivo.
CONCLUSIONS
These results highlight that tumour-derived sEVs function as a bridge between peripheral immunity regulation and the tumour microenvironment, and contribute to cancer progression through altering the composition and function of the global immune macroenvironment.
背景
肿瘤来源的小细胞外囊泡（sEVs）在癌症免疫调节中起着至关重要的作用。除了肿瘤免疫微环境外，外周免疫系统也对癌症的进展有重大贡献，是抗癌免疫所必需的。然而，肿瘤来源的 sEVs 在癌症发展过程中如何以及调控哪些外周免疫谱系的全面定义仍不完整。
方法
在这项研究中，我们使用了广泛的抗体面板的质谱流式细胞术，全面构建了系统免疫景观以响应肿瘤的发展和肿瘤来源的 sEVs。
结果
肿瘤的生长和肿瘤来源的 sEVs 极大地改变了系统免疫。肿瘤来源的 sEVs 显著且广泛地影响了免疫细胞群体组成和细胞内途径，导致了抑制性的外周和肿瘤免疫微环境，表现为髓系来源的抑制细胞增加和 Ly6CCD8 T 细胞减少。这些 sEVs 极大地促进了造血恢复，并加速了向髓系来源的抑制细胞的分化。Rab27a 的敲低减少了肿瘤细胞中 sEV 的分泌，并延迟了体内肿瘤的生长和转移。
结论
这些结果强调了肿瘤来源的 sEVs 作为外周免疫调节和肿瘤微环境之间的桥梁的功能，并通过改变全局免疫宏观环境的组成和功能来促进癌症的进展。
Zotero 插件