Lymphocyte access to lymphoma is impaired by high endothelial venule regression - Aix-Marseille Université Access content directly
Journal Articles Cell Reports Year : 2021

Lymphocyte access to lymphoma is impaired by high endothelial venule regression

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.
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hal-03565977 , version 1 (24-10-2022)

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Lutz Menzel, Maria Zschummel, Tadhg Crowley, Vedran Franke, Michael Grau, et al.. Lymphocyte access to lymphoma is impaired by high endothelial venule regression. Cell Reports, 2021, 37 (4), pp.109878. ⟨10.1016/j.celrep.2021.109878⟩. ⟨hal-03565977⟩
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