Toll-like Receptor-4 Activation Boosts the Immunosuppressive Properties of Tumor Cells-derived Exosomes
Toll-like Receptor-4 Activation Boosts the Immunosuppressive Properties of Tumor Cells-derived Exosomes
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DOI：
10.1038/s41598-019-44949-y
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发表时间：
2019-06-11
影响因子：
4.6
通讯作者：
Curcio, Francesco
中科院分区：
文献类型：
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作者：
Domenis, Rossana;Cifu, Adriana;Curcio, Francesco
肿瘤来源的外切体(Tex)的生物学特性尚不完全清楚，仍需进一步研究，以明确肿瘤微环境或肿瘤细胞的激活对其组成和功能的影响。在慢性感染和炎症条件下，Toll样受体4的表达和活性增加与癌症的进展有关：它的激活诱导了一种炎症信号，从而增加了癌细胞的致瘤潜能，促进了它们的免疫逃避。我们研究了细胞TLR4激活时释放的Tex的免疫调节特性，我们发现，尽管根据肿瘤类型的不同而观察到不同的治疗方法，但治疗影响Tex的组成并增强其免疫抑制能力。我们的结果表明，TLR4的激活通过刺激更有效的免疫抑制外体的释放来支持肿瘤的进展，这些外体允许肿瘤细胞逃避免疫监视，甚至可能在转移过程中发挥作用。
The biology of tumor-derived exosomes (TEX) is only partially understood and much remains to be studied in order to define the effect that the tumor microenvironment or the activation of tumor cells exerts on their composition and functions. Increased expression and activity of toll-like receptor 4 (TLR4) in chronic infectious and inflammatory conditions is related with cancer progression: its activation induces an inflammatory signaling that increases the tumorigenic potential of cancer cells promoting their immune evasion. We investigated the immune modulatory properties of TEX released upon cell TLR4 activation, and we found that, although differences were observed depending on the type of the tumor, the treatment influences TEX composition and boosts their immunosuppressive ability. Our results suggest that the activation of TLR4 supports tumor progression by stimulating the release of more effective immunosuppressive exosomes, which allow tumor cells to escape immune surveillance and probably even play a role in the metastatic process.