Karakousi Triantafyllia, Mudianto Tenny, Lund Amanda W
Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, New York, NY, USA.
Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Nat Rev Cancer. 2024 Jun;24(6):363-381. doi: 10.1038/s41568-024-00681-y. Epub 2024 Apr 11.
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.
淋巴转运维持着体内稳态健康,是免疫监视所必需的,然而淋巴管生长常常与实体瘤的发展和扩散相关。尽管肿瘤相关的淋巴管重塑和生长最初被认为只是为区域转移扩展了一条被动途径,但新出现的研究将淋巴管及其主动转运置于转移、肿瘤相关炎症和全身免疫监视的界面。在这里,我们讨论淋巴管塑造其转运功能以影响外周组织免疫的主动机制,以及目前对肿瘤相关淋巴管如何既能增强又能破坏抗肿瘤免疫监视的理解。最后,我们展望癌症免疫治疗领域中新兴的研究热点,其中淋巴管及其转运功能可能是关键因素:三级淋巴结构的形成、中枢神经系统中的免疫监视、微生物群、肥胖和衰老。所汲取的经验支持了一个工作框架,该框架将淋巴系统定义为局部和全身炎症网络的关键决定因素,从而也是癌症免疫治疗反应中的关键参与者。