Lymphatic vessels in the age of cancer immunotherapy

Abstract

Lymphatic transport maintains homeostatic health and is necessary for immune surveillance, and yet lymphatic growth is often associated with solid tumour development and dissemination. Although tumour-associated lymphatic remodelling and growth were initially presumed to simply expand a passive route for regional metastasis, emerging research puts lymphatic vessels and their active transport at the interface of metastasis, tumour-associated inflammation and systemic immune surveillance. Here, we discuss active mechanisms through which lymphatic vessels shape their transport function to influence peripheral tissue immunity and the current understanding of how tumour-associated lymphatic vessels may both augment and disrupt antitumour immune surveillance. We end by looking forward to emerging areas of interest in the field of cancer immunotherapy in which lymphatic vessels and their transport function are likely key players: the formation of tertiary lymphoid structures, immune surveillance in the central nervous system, the microbiome, obesity and ageing. The lessons learnt support a working framework that defines the lymphatic system as a key determinant of both local and systemic inflammatory networks and thereby a crucial player in the response to cancer immunotherapy. Tumour-associated lymphatic growth and remodelling were once viewed as a passive means by which cancer cells could regionally spread to lymph nodes. However, recent data point to an active and contrasting role for lymphatic vessels and their transport in antitumour immune surveillance. In this Review, Karakousi et al. provide a working framework to define this role for the lymphatic system in tumour progression and present avenues for its therapeutic manipulation to improve cancer immunotherapy.