Departments of Pathology, Immunology and Otolaryngology, University of Pittsburgh School of Medicine and UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA.
Cells. 2021 Nov 6;10(11):3054. doi: 10.3390/cells10113054.
Emerging studies suggest that extracellular vesicles (EVs) mediating intercellular communication in the tumor microenvironment (TME) play a key role in driving cancer progression. Tumor-derived small EVs or exosomes (TEX) enriched in immunosuppressive proteins or in microRNAs targeting suppressive pathways in recipient cells contribute to reprogramming the TME into a cancer-promoting milieu. The adenosinergic pathway is an acknowledged major contributor to tumor-induced immune suppression. TEX carry the components of this pathway and utilize ATP to produce adenosine (ADO). TEX-associated ADO emerges as a key factor in the suppression of T cell responses to therapy. Here, the significance of the ADO pathway in TEX is discussed as a highly effective mechanism of cancer-driven immune cell suppression and of resistance to immune therapies.
新兴研究表明,细胞外囊泡(EVs)在肿瘤微环境(TME)中介导细胞间通讯,在推动癌症进展方面发挥着关键作用。富含免疫抑制蛋白或针对受体细胞中抑制途径的 microRNAs 的肿瘤衍生小 EVs 或外泌体(TEX)有助于将 TME 重塑为促进癌症的环境。腺苷能途径是公认的肿瘤诱导免疫抑制的主要贡献者。TEX 携带该途径的成分,并利用 ATP 产生腺苷(ADO)。TEX 相关的 ADO 作为抑制 T 细胞对治疗反应的关键因素出现。本文讨论了 ADO 途径在 TEX 中的重要性,认为这是癌症驱动免疫细胞抑制和对免疫治疗产生耐药性的一种非常有效的机制。