2026-04-29T19:34:57Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/272542026-02-22T01:20:52Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Leary, Noelle author Walser, Sarina author He, Yuliang author Cousin, Nikola author Pereira, Paulo author Gallo, Alessandro author Collado-Diaz, Victor author Halin, Cornelia author Garcia-Silva, Susana author Peinado Selgas, Hector author Dieterich, Lothar C author 2022-02 Tumour-draining lymph nodes (LNs) undergo massive remodelling including expansion of the lymphatic sinuses, a process that has been linked to lymphatic metastasis by creation of a pre-metastatic niche. However, the signals leading to these changes have not been completely understood. Here, we found that extracellular vesicles (EVs) derived from melanoma cells are rapidly transported by lymphatic vessels to draining LNs, where they selectively interact with lymphatic endothelial cells (LECs) as well as medullary sinus macrophages. Interestingly, uptake of melanoma EVs by LN-resident LECs was partly dependent on lymphatic VCAM-1 expression, and induced transcriptional changes as well as proliferation of those cells. Furthermore, melanoma EVs shuttled tumour antigens to LN LECs for cross-presentation on MHC-I, resulting in apoptosis induction in antigen-specific CD8 T cells. In conclusion, our data identify EV-mediated melanoma-LN LEC communication as a new pathway involved in tumour progression and tumour immune inhibition, suggesting that EV uptake or effector mechanisms in LECs might represent a new target for melanoma therapy. J Extracell Vesicles . 2022 Feb;11(2):e12197. J Extracell Vesicles 35188342 https://hdl.handle.net/20.500.12105/27254 exosome immunotherapy lymphangiogenesis pre-metastatic niche sentinel lymph node Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.