Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles
Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles
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DOI：
10.1016/j.celrep.2019.05.008
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发表时间：
2019-06-04
期刊：
影响因子：
8.8
通讯作者：
De Palma, Michele
中科院分区：
文献类型：
--
作者：
Cianciaruso, Chiara;Beltraminelli, Tim;De Palma, Michele
细胞外囊泡（EV），包括外来体，调节癌症生物学的多个方面。肿瘤相关巨噬细胞（TAMs）分泌EV，但其分子特征和功能的特征很差。在这里，我们报告的方法富集，定量，蛋白质组学和脂质组学分析的EV释放从小鼠TAM（TAM-EV）。与来源TAM相比，TAM-EV呈现与Th 1/M1极化特征、增强的炎症和免疫应答以及更有利的患者预后相关的分子谱。因此，富集的TAM-EV制剂促进离体T细胞增殖和活化。TAM-EV还含有生物活性脂质和生物合成酶，这可能会改变癌细胞中的促炎信号。因此，尽管TAM在很大程度上是免疫抑制性的，但它们的EV可能具有刺激而不是限制抗肿瘤免疫的潜力。
Extracellular vesicles (EVs), including exosomes, modulate multiple aspects of cancer biology. Tumor-associated macrophages (TAMs) secrete EVs, but their molecular features and functions are poorly characterized. Here, we report methodology for the enrichment, quantification, and proteomic and lipidomic analysis of EVs released from mouse TAMs (TAM-EVs). Compared to source TAMs, TAM-EVs present molecular profiles associated with a Th1/M1 polarization signature, enhanced inflammation and immune response, and a more favorable patient prognosis. Accordingly, enriched TAM-EV preparations promote T cell proliferation and activation ex vivo. TAM-EVs also contain bioactive lipids and biosynthetic enzymes, which may alter pro-inflammatory signaling in the cancer cells. Thus, whereas TAMs are largely immunosuppressive, their EVs may have the potential to stimulate, rather than limit, anti-tumor immunity.