Tumor growth and progression require molecular interactions between malignant and host cells. In recent years, extracellular vesicles (EVs) emerged as an important pillar of such interactions, carrying molecular information from their donor cells to distant recipient cells. Thereby, the phenotype and function of the recipient cells are altered, which may facilitate tumor immune escape and tumor metastasis to other organs through the formation of pre-metastatic niches. A prerequisite for these effects of tumor cell-derived EVs is an efficient transport system from the site of origin to the body periphery. Here, we highlight the role of the lymphatic vascular system in the distribution and progression-promoting functions of tumor cell-derived EVs. Importantly, the lymphatic vascular system is the primary drainage system for interstitial fluid and its soluble, particulate, and cellular contents, and therefore represents the principal route for regional (i.e., to tumor-draining lymph nodes) and systemic distribution of EVs derived from solid tumors. Furthermore, recent studies highlighted the tumor-draining lymph node as a crucial site where tumor-derived EVs exert their effects. A deeper mechanistic understanding of how EVs gain access to the lymphatic vasculature, how they interact with their recipient cells in tumor-draining lymph nodes and beyond, and how they induce phenotypic and functional maladaptation will be instrumental to identify new molecular targets and conceive innovative approaches for cancer therapy.
肿瘤的生长与进展需要恶性细胞与宿主细胞之间的分子相互作用。近年来，细胞外囊泡作为此类相互作用的重要载体，可将供体细胞的分子信息传递至远端受体细胞，从而改变受体细胞的表型和功能，可能通过形成转移前微环境促进肿瘤免疫逃逸及向其他器官转移。肿瘤来源细胞外囊泡发挥这些效应的前提是具备从起源部位到机体外周的高效运输系统。本文重点探讨淋巴管系统在肿瘤来源细胞外囊泡的分布及促进展功能中的作用。值得注意的是，淋巴管系统是组织液及其可溶性成分、颗粒物与细胞内容物的主要引流通道，因此成为实体瘤来源细胞外囊泡实现区域性和全身性分布的主要途径。最新研究进一步揭示，肿瘤引流淋巴结是肿瘤来源细胞外囊泡发挥功能的关键场所。深入理解细胞外囊泡如何进入淋巴管系统、如何在肿瘤引流淋巴结及其他部位与受体细胞相互作用，以及如何诱导表型与功能适应不良，将有助于发现新的分子靶点并设计创新的癌症治疗策略。
The Lymphatic Vascular System in Extracellular Vesicle-Mediated Tumor Progression
肿瘤(癌症)患者之家