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Menzel L, Zschummel M, Crowley T, et al. Lymphocyte access to lymphoma is impaired by high endothelial venule regression. Cell Rep. 2021;37(4):109878doi: 10.1016/j.celrep.2021.109878.
Menzel, L., Zschummel, M., Crowley, T., Franke, V., Grau, M., Ulbricht, C., Hauser, A., Siffrin, V., Bajénoff, M., Acton, S. E., Akalin, A., Lenz, G., Willimsky, G., Höpken, U. E., & Rehm, A. (2021). Lymphocyte access to lymphoma is impaired by high endothelial venule regression. Cell reports, 37(4), 109878. https://doi.org/10.1016/j.celrep.2021.109878
Menzel, Lutz, et al. "Lymphocyte access to lymphoma is impaired by high endothelial venule regression." Cell reports vol. 37,4 (2021): 109878. doi: https://doi.org/10.1016/j.celrep.2021.109878
Menzel L, Zschummel M, Crowley T, Franke V, Grau M, Ulbricht C, Hauser A, Siffrin V, Bajénoff M, Acton SE, Akalin A, Lenz G, Willimsky G, Höpken UE, Rehm A. Lymphocyte access to lymphoma is impaired by high endothelial venule regression. Cell Rep. 2021 Oct 26;37(4):109878. doi: 10.1016/j.celrep.2021.109878. PMID: 34706240; PMCID: PMC8567313.
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Cell Rep. 2021 Oct 26;37(4):109878. doi: 10.1016/j.celrep.2021.109878.

Lymphocyte access to lymphoma is impaired by high endothelial venule regression.

Cell reports

Lutz Menzel, Maria Zschummel, Tadhg Crowley, Vedran Franke, Michael Grau, Carolin Ulbricht, Anja Hauser, Volker Siffrin, Marc Bajénoff, Sophie E Acton, Altuna Akalin, Georg Lenz, Gerald Willimsky, Uta E Höpken, Armin Rehm

Affiliations

  1. Translational Tumorimmunology, Max-Delbrück-Center for Molecular Medicine Berlin, Germany, 13125 Berlin, Germany.
  2. Microenvironmental Regulation in Autoimmunity and Cancer, Max-Delbrück-Center for Molecular Medicine Berlin, 13125 Berlin, Germany.
  3. Neuroimmunology Laboratory, Max-Delbrück-Center for Molecular Medicine Berlin, Germany, 13125 Berlin, Germany.
  4. Bioinformatics & Omics Data Science Platform, BIMSB at Max-Delbrück-Center for Molecular Medicine Berlin, 13125 Berlin, Germany.
  5. Medical Department A for Hematology, Oncology, and Pneumology, University Hospital Münster, 48149 Münster, Germany.
  6. Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Rheumatology and Clinical Immunology, and Immune Dynamics, Deutsches Rheumaforschungszentrum Berlin, 10117 Berlin, Germany.
  7. Neuroimmunology Laboratory, Max-Delbrück-Center for Molecular Medicine Berlin, Germany, 13125 Berlin, Germany; Neuroimmunology Laboratory, Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany.
  8. Aix Marseille University, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, 13288 Marseille, France.
  9. Stromal Immunology Group, MRC Laboratory for Molecular Cell Biology, University College London, WC1E 6BT London, UK.
  10. Institute of Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13125 Berlin, Germany; German Cancer Research Center, 69120 Heidelberg, Germany; German Cancer Consortium, partner site Berlin, Germany.
  11. Translational Tumorimmunology, Max-Delbrück-Center for Molecular Medicine Berlin, Germany, 13125 Berlin, Germany. Electronic address: [email protected].

PMID: 34706240 PMCID: PMC8567313 DOI: 10.1016/j.celrep.2021.109878

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.

Copyright © 2021 Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association. Published by Elsevier Inc. All rights reserved.

Keywords: B cell lymphoma; angiogenesis; blood endothelial cells; chemokines; dendritic cells; high endothelial venules; immune cell trafficking; immunosurveillance; lymphotoxin beta-receptor; tumor stroma

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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