Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention

Publication date: 16 September 2019Source: Cancer Cell, Volume 36, Issue 3Author(s): Tracy O'Connor, Xiaolan Zhou, Jan Kosla, Arlind Adili, Maria Garcia Beccaria, Elena Kotsiliti, Dominik Pfister, Anna-Lena Johlke, Ankit Sinha, Roman Sankowski, Markus Schick, Richard Lewis, Nikolaos Dokalis, Bastian Seubert, Bastian Höchst, Donato Inverso, Danijela Heide, Wenlong Zhang, Petra Weihrich, Katrin ManskeSummaryHow 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.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research