Menzel, L;
Zschummel, M;
Crowley, T;
Franke, V;
Grau, M;
Ulbricht, C;
Hauser, A;
... Rehm, A; + view all
(2021)
Lymphocyte access to lymphoma is impaired by high endothelial venule regression.
Cell Reports
, 37
(4)
, Article 109878. 10.1016/j.celrep.2021.109878.
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Abstract
Blood endothelial cells display remarkable plasticity depending on the demands of a malignant microenvironment. While studies in solid tumors focus on their role in metabolic adaptations, formation of high endothelial venules (HEVs) in lymph nodes extends their role to the organization of immune cell interactions. As a response to lymphoma growth, blood vessel density increases; however, the fate of HEVs remains elusive. Here, we report that lymphoma causes severe HEV regression in mouse models that phenocopies aggressive human B cell lymphomas. HEV dedifferentiation occurrs as a consequence of a disrupted lymph-carrying conduit system. Mechanosensitive fibroblastic reticular cells then deregulate CCL21 migration paths, followed by deterioration of dendritic cell proximity to HEVs. Loss of this crosstalk deprives HEVs of lymphotoxin-β-receptor (LTβR) signaling, which is indispensable for their differentiation and lymphocyte transmigration. Collectively, this study reveals a remodeling cascade of the lymph node microenvironment that is detrimental for immune cell trafficking in lymphoma.
| Type: | Article |
|---|---|
| Title: | Lymphocyte access to lymphoma is impaired by high endothelial venule regression |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2021.109878 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2021.109878 |
| Language: | English |
| Additional information: | © 2021 Max-Delbru¨ ck-Center for Molecular Medicine in the Helmholtz Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | B cell lymphoma, high endothelial venules, blood endothelial cells, immunosurveill, anceangiogenesis, tumor stroma, immune cell trafficking, chemokines, lymphotoxin beta-receptor, dendritic cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10141465 |
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