Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
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...
| Authors: | ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2022 |
| Country: | España |
| Institution: | Instituto de Salud Carlos III (ISCIII) |
| Repository: | Repisalud |
| Language: | English |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/27254 |
| Online Access: | https://hdl.handle.net/20.500.12105/27254 |
| Access Level: | Open access |
| Keyword: | exosome immunotherapy lymphangiogenesis pre-metastatic niche sentinel lymph node |
| _version_ | 1878732182790340608 |
|---|---|
| author | Leary, Noelle |
| author2 | Walser, Sarina He, Yuliang Cousin, Nikola Pereira, Paulo Gallo, Alessandro Collado-Diaz, Victor Halin, Cornelia Garcia-Silva, Susana Peinado Selgas, Hector Dieterich, Lothar C |
| author2_role | author author author author author author author author author author |
| author_browse | Collado-Diaz, Victor Cousin, Nikola Dieterich, Lothar C Gallo, Alessandro Garcia-Silva, Susana Halin, Cornelia He, Yuliang Leary, Noelle Peinado Selgas, Hector Pereira, Paulo Walser, Sarina |
| author_facet | Leary, Noelle Walser, Sarina He, Yuliang Cousin, Nikola Pereira, Paulo Gallo, Alessandro Collado-Diaz, Victor Halin, Cornelia Garcia-Silva, Susana Peinado Selgas, Hector Dieterich, Lothar C |
| author_role | author |
| collection | Repisalud |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_3e1ed8b2ea21faac627cd4e2c23f43d7 |
| institution | Instituto de Salud Carlos III (ISCIII) |
| instname_str | Instituto de Salud Carlos III (ISCIII) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repisalud.isciii.es:20.500.12105/27254 |
| publishDate | 2022 |
| publishDateSort | 2022 |
| publisher | Wiley |
| publisherStr | Wiley |
| reponame_str | Repisalud |
| spelling | Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. Leary, Noelle Walser, Sarina He, Yuliang Cousin, Nikola Pereira, Paulo Gallo, Alessandro Collado-Diaz, Victor Halin, Cornelia Garcia-Silva, Susana Peinado Selgas, Hector Dieterich, Lothar C exosome immunotherapy lymphangiogenesis pre-metastatic niche sentinel lymph node 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. Wiley https://hdl.handle.net/20.500.12105/27254 |
| spellingShingle | Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. Leary, Noelle exosome immunotherapy lymphangiogenesis pre-metastatic niche sentinel lymph node |
| title | Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. |
| title_full | Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. |
| title_fullStr | Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. |
| title_full_unstemmed | Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. |
| title_short | Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. |
| title_sort | Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. |
| topic | exosome immunotherapy lymphangiogenesis pre-metastatic niche sentinel lymph node |
| topic_facet | exosome immunotherapy lymphangiogenesis pre-metastatic niche sentinel lymph node |
| url | https://hdl.handle.net/20.500.12105/27254 |