A Quest for the Dual Role of Lymphatic Transport in Cancer: From Immune Surveillance to Tumour Dissemination

Background: Lymphatic transport is indispensable for maintaining tissue homeostasis and orchestrating immune surveillance. However, its association with solid tumor development and dissemination poses a paradox. While initially perceived as a passive conduit for metastasis, recent research highlights the active involvement of lymphatic vessels in tumor progression, inflammation, and immune surveillance. Objective: This study aims to elucidate the active mechanisms underlying lymphatic transport's contribution to peripheral tissue immunity and its dual role in tumor-associated immune responses. Additionally, it explores emerging areas of interest in targeted cancer immunotherapy. Methods: A comprehensive literature review was conducted to gather insights into the role of lymphatic transport in both physiological and pathological contexts, with a focus on cancer progression and immune modulation. Relevant studies and reviews were analyzed to provide current understanding and identify future directions in cancer immunotherapy. Results: Lymphatic vessels actively shape their transport function to influence peripheral tissue immunity, facilitating immune cell trafficking and antigen drainage. However, tumor-associated lymphatic remodeling disrupts this balance, promoting tumor dissemination and fostering a protumorigenic microenvironment. Emerging research implicates lymphatic vessels in the formation of tertiary lymphoid structures, immune surveillance in the central nervous system, and interactions with the microbiome, obesity, and aging, highlighting their multifaceted role in cancer immunity. Conclusion: Insights gained in lymphatic biology offer promising avenues for enhancing cancer immunotherapy by targeting lymphatic vessels and their transport function. A comprehensive understanding of lymphatic involvement in cancer pathogenesis supports its integration into therapeutic strategies to optimize immune surveillance and improve patient outcomes.