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Age-related gliosis promotes central nervous system lymphoma through CCL19-mediated tumor cell retention

Item Type:Article
Title:Age-related gliosis promotes central nervous system lymphoma through CCL19-mediated tumor cell retention
Creators Name:O'Connor, T. and Zhou, X. and Kosla, J. and Adili, A. and Garcia Beccaria, M. and Kotsiliti, E. and Pfister, D. and Johlke, A.L. and Sinha, A. and Sankowski, R. and Schick, M. and Lewis, R. and Dokalis, N. and Seubert, B. and Höchst, B. and Inverso, D. and Heide, D. and Zhang, W. and Weihrich, P. and Manske, K. and Wohlleber, D. and Anton, M. and Hoellein, A. and Seleznik, G. and Bremer, J. and Bleul, S. and Augustin, H.G. and Scherer, F. and Koedel, U. and Weber, A. and Protzer, U. and Förster, R. and Wirth, T. and Aguzzi, A. and Meissner, F. and Prinz, M. and Baumann, B. and Höpken, U.E. and Knolle, P.A. and von Baumgarten, L. and Keller, U. and Heikenwalder, M.
Abstract:How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-κB-induced gliosis promotes CNSL in immunocompetent mice. Gliosis elevated cell-adhesion molecules, which increased LCs in the brain but was insufficient to induce CNSL. Astrocyte-derived CCL19 was required for gliosis-induced CNSL. Deleting CCL19 in mice or CCR7 from LCs abrogated CNSL development. Two-photon microscopy revealed LCs transiently entering normal brain parenchyma. Astrocytic CCL19 enhanced parenchymal CNS retention of LCs, thereby promoting CNSL formation. Aged, gliotic wild-type mice were more susceptible to forming CNSL than young wild-type mice, and astrocytic CCL19 was observed in both human gliosis and CNSL. Therefore, CCL19-CCR7 interactions may underlie an increased age-related risk for CNSL.
Keywords:CNSL, PCNSL, SCNSL, Gliosis, CCL19, Metastasis, Lymphoma, DLBCL, Neuroinflammation, CXCL12, Animals, Mice
Source:Cancer Cell
ISSN:1535-6108
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:36
Number:3
Page Range:250-267
Date:16 September 2019
Official Publication:https://doi.org/10.1016/j.ccell.2019.08.001
PubMed:View item in PubMed

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