The lymphatic vasculature has been widely described and explored for its key functions in fluid homeostasis and in the organization and modulation of the immune response. Besides transporting immune cells, lymphatic vessels play relevant roles in tumor growth and tumor cell dissemination. Cancer cells that have invaded into afferent lymphatics are propagated to tumor-draining lymph nodes (LNs), which represent an important hub for metastatic cell arrest and growth, immune modulation, and secondary dissemination to distant sites. In recent years many studies have reported new mechanisms by which the lymphatic vasculature affects cancer progression, ranging from induction of lymphangiogenesis to metastatic niche preconditioning or immune modulation. In this review, we provide an up-to-date description of lymphatic organization and function in peripheral tissues and in LNs and the changes induced to this system by tumor growth and progression. We will specifically focus on the reported interactions that occur between tumor cells and lymphatic endothelial cells (LECs), as well as on interactions between immune cells and LECs, both in the tumor microenvironment and in tumor-draining LNs. Moreover, the most recent prognostic and therapeutic implications of lymphatics in cancer will be reported and discussed in light of the new immune-modulatory roles that have been ascribed to LECs.

中文翻译：

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淋巴脉管系统：癌症进展中的积极和动态参与者

淋巴脉管系统因其在液体稳态以及免疫反应的组织和调节中的关键功能而被广泛描述和探索。除了运输免疫细胞外，淋巴管在肿瘤生长和肿瘤细胞传播中也发挥着重要作用。侵入传入淋巴管的癌细胞传播到肿瘤引流淋巴结 (LN)，这是转移性细胞停滞和生长、免疫调节和二次传播到远处部位的重要枢纽。近年来，许多研究报告了淋巴脉管系统影响癌症进展的新机制，范围从诱导淋巴管生成到转移性生态位预处理或免疫调节。在本次审查中，我们提供了外周组织和 LN 中淋巴组织和功能的最新描述，以及肿瘤生长和进展对该系统引起的变化。我们将特别关注肿瘤细胞和淋巴管内皮细胞 (LEC) 之间发生的相互作用，以及免疫细胞和 LEC 之间的相互作用，无论是在肿瘤微环境中还是在肿瘤引流 LNs 中。此外，将根据已归因于 LEC 的新免疫调节作用报告和讨论淋巴管在癌症中的最新预后和治疗意义。以及肿瘤微环境和肿瘤引流LNs中免疫细胞和LECs之间的相互作用。此外，将根据已归因于 LEC 的新免疫调节作用报告和讨论淋巴管在癌症中的最新预后和治疗意义。以及肿瘤微环境和肿瘤引流LNs中免疫细胞和LECs之间的相互作用。此外，将根据已归因于 LEC 的新免疫调节作用报告和讨论淋巴管在癌症中的最新预后和治疗意义。