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

O'Connor, T.; Zhou, X.; Kosla, J.; Adili, A.; Garcia Beccaria, M.; Kotsiliti, E.; Pfister, D.; Johlke, A.L.; Sinha, A.; Sankowski, R.; Schick, M.; Lewis, R.; Dokalis, N.; Seubert, B.; Höchst, B.; Inverso, D.; Heide, D.; Zhang, W.; Weihrich, P.; Manske, K.; Wohlleber, D.; Anton, M.; Hoellein, A.; Seleznik, G.; Bremer, J.; Bleul, S.; Augustin, H.G.; Scherer, F.; Koedel, U.; Weber, A.; Protzer, U.; Förster, R.; Wirth, T.; Aguzzi, A.; Meissner, F.; Prinz, M.; Baumann, B.; Höpken, U.E.; Knolle, P.A.; von Baumgarten, L.; Keller, U.; Heikenwalder, M.

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

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Item Type:	Article
Title:	Age-related gliosis promotes central nervous system lymphoma through CCL19-mediated tumor cell retention
Creators:	O'Connor, T., Zhou, X., Kosla, J., Adili, A., Garcia Beccaria, M., Kotsiliti, E., Pfister, D., Johlke, A.L., Sinha, A., Sankowski, R., Schick, M. ORCID: https://orcid.org/0009-0003-8626-0611, Lewis, R., Dokalis, N., Seubert, B., Höchst, B., Inverso, D., Heide, D., Zhang, W., Weihrich, P., Manske, K., Wohlleber, D., Anton, M., Hoellein, A., Seleznik, G., Bremer, J., Bleul, S., Augustin, H.G., Scherer, F., Koedel, U., Weber, A., Protzer, U., Förster, R., Wirth, T., Aguzzi, A., Meissner, F., Prinz, M., Baumann, B., Höpken, U.E. ORCID: https://orcid.org/0000-0002-0776-4893, Knolle, P.A., von Baumgarten, L., Keller, U. ORCID: https://orcid.org/0000-0002-8485-1958 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
Volume:	36
Number:	3
Page Range:	250-267
Date:	16 September 2019
Additional Information:	Erratum in: Cancer Cell 2025 Jul 3.
Official Publication:	https://doi.org/10.1016/j.ccell.2019.08.001
PubMed:	View item in PubMed

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