Abstract：
Tumor-derived extracellular vesicles (EVs) are one of the most important ways of intercellular communication and signaling. Cancer stem cells (CSCs) secrete EVs to modulate immune checkpoint molecules and evade immune surveillance. Activated CD8+ T cells known as cytotoxic T lymphocytes (CTLs) are the most powerful anti-cancer adaptive cells. Their activity is compromised upon encountering cells and signaling within the tumor microenvironment (TME), resulting in hyporesponsiveness called exhaustion. CSC-derived exosomes express programmed death ligand-1 (PD-L1) and upregulate programmed death-1 (PD-1) on CD8+ T cells to promote their exhaustion. PD-L1 expression on tumor-derived exosomes appears to be induced by CSC-derived exosomes containing transforming growth factor (TGF)-β. Tenascin-C is another constituent of CSC exosomes that acts on mammalian target of rapamycin (mTOR) signaling in T cells. Glycolysis is a metabolic event promoted by the inducing effect of CSC-derived exosomes on hypoxia-inducible factor-1α (HIF-1α). CSC interaction with CD8+ T cells is even more complex as the CSC-derived exosomes contain Notch1 to stimulate stemness in non-tumor cells, and the inducible effect of Notch1 on PD-1 promotes CD8+ T cell exhaustion. CSC exosome targeting has not been extensively studied yet. Advances in the field will open up new therapeutic windows and shape the future of cancer immunotherapy.
摘要：
肿瘤来源的细胞外囊泡（EV）是细胞间通讯和信号传导的最重要方式之一。癌症干细胞（CSC）分泌EV以调节免疫检查点分子并逃避免疫监视。被称为细胞毒性T淋巴细胞(CTL)的活化CD8+T细胞是最强大的抗癌适应性细胞。它们的活性在肿瘤微环境（TME）内遇到细胞和信号时受到损害，导致反应不足，称为精疲力竭。CSC衍生的外泌体在CD8+T细胞上表达程序性死亡配体-1(PD-L1)并上调程序性死亡-1(PD-1)以促进其耗尽。肿瘤衍生的外泌体上的PD-L1表达似乎由含有转化生长因子(TGF)-β的CSC衍生的外泌体诱导。生腱蛋白-C是CSC外泌体的另一种成分,其作用于T细胞中的哺乳动物雷帕霉素靶标(mTOR)信号传导。糖酵解是由CSC衍生的外泌体对缺氧诱导因子-1α（HIF-1α）的诱导作用促进的代谢事件。CSC与CD8+T细胞的相互作用更加复杂，因为CSC衍生的外泌体含有Notch1以刺激非肿瘤细胞的干性，Notch1对PD-1的诱导作用促进CD8+T细胞衰竭。CSC外泌体靶向尚未被广泛研究。该领域的进展将打开新的治疗窗口，并塑造癌症免疫治疗的未来。
