Whiteside Theresa L
Pathology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
J Immunother Cancer. 2025 Jan 23;13(1):e010376. doi: 10.1136/jitc-2024-010376.
Extracellular vesicles (EVs) are produced by all living cells and are present in all body fluids. EVs are heterogeneous in size, biogenesis, molecular/genetic content and functions. They constitute a part of the intercellular communication system. Among them, a subset of small EVs (sEVs) (30-150 nm) originating in the tumor cell endosomes and often referred to as "tumor cell-derived exosomes" have been of special interest. Tumors have adapted sEV they produce to promoting their own survival. Plasma of patients with cancer contains variably elevated numbers of tumor-derived sEV called "TEX," which differ from circulating sEV produced by non-malignant cells by the immunosuppressive phenotype and the molecular/genetic content. Immunosuppressive molecular profiles and abilities to signal, enter and functionally reprogram a variety of recipient cells enable TEX to exert pro-tumor effects that promote tumor resistance to immunotherapy. This review describes phenotypic and functional attributes of TEX that underline their reprogramming capabilities. It also considers mechanisms responsible for TEX pro-tumor activities and the potential significance of TEX signaling for responses of patients with cancer to immune therapies.
细胞外囊泡(EVs)由所有活细胞产生,存在于所有体液中。EVs在大小、生物发生、分子/遗传内容和功能方面具有异质性。它们构成细胞间通讯系统的一部分。其中,起源于肿瘤细胞内体的一小部分小EVs(sEVs,30 - 150纳米),常被称为“肿瘤细胞衍生外泌体”,特别受关注。肿瘤已经使其产生的sEV适应于促进自身存活。癌症患者的血浆中含有数量不等且升高的肿瘤衍生sEV,称为“TEX”,其与非恶性细胞产生的循环sEV在免疫抑制表型和分子/遗传内容上有所不同。免疫抑制分子谱以及向多种受体细胞发出信号、进入并在功能上对其进行重编程的能力,使TEX能够发挥促肿瘤作用,促进肿瘤对免疫治疗的抵抗。本综述描述了TEX的表型和功能特性,这些特性突出了它们的重编程能力。它还考虑了TEX促肿瘤活性的机制以及TEX信号传导对癌症患者免疫治疗反应的潜在意义。
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