Santos Nathalia Leal, Bustos Silvina Odete, Bhatt Darshak, Chammas Roger, Andrade Luciana Nogueira de Sousa
Center for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Front Cell Dev Biol. 2021 Aug 31;9:737449. doi: 10.3389/fcell.2021.737449. eCollection 2021.
Cancer can be described as a dynamic disease formed by malignant and stromal cells. The cellular interaction between these components in the tumor microenvironment (TME) dictates the development of the disease and can be mediated by extracellular vesicles secreted by tumor cells (TEVs). In this review, we summarize emerging findings about how TEVs modify important aspects of the disease like continuous tumor growth, induction of angiogenesis and metastasis establishment. We also discuss how these nanostructures can educate the immune infiltrating cells to generate an immunosuppressive environment that favors tumor progression. Furthermore, we offer our perspective on the path TEVs interfere in cancer treatment response and promote tumor recurrence, highlighting the need to understand the underlying mechanisms controlling TEVs secretion and cargo sorting. In addition, we discuss the clinical potential of TEVs as markers of cell state transitions including the acquisition of a treatment-resistant phenotype, and their potential as therapeutic targets for interventions such as the use of extracellular vesicle (EV) inhibitors to block their pro-tumoral activities. Some of the technical challenges for TEVs research and clinical use are also presented.
癌症可被描述为一种由恶性细胞和基质细胞形成的动态疾病。肿瘤微环境（TME）中这些成分之间的细胞相互作用决定了疾病的发展，并且可由肿瘤细胞分泌的细胞外囊泡（TEV）介导。在本综述中，我们总结了关于TEV如何改变疾病重要方面（如肿瘤持续生长、诱导血管生成和建立转移）的新发现。我们还讨论了这些纳米结构如何影响免疫浸润细胞以产生有利于肿瘤进展的免疫抑制环境。此外，我们阐述了TEV干扰癌症治疗反应并促进肿瘤复发的途径，强调了理解控制TEV分泌和货物分选的潜在机制的必要性。此外，我们讨论了TEV作为细胞状态转变标志物（包括获得治疗抗性表型）的临床潜力，以及它们作为治疗靶点（如使用细胞外囊泡（EV）抑制剂来阻断其促肿瘤活性）的潜力。还介绍了TEV研究和临床应用的一些技术挑战。
