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

O'Connor, Tracy; Zhou, Xiaolan; Kosla, Jan; Adili, Arlind; Beccaria, Maria Garcia; Kotsiliti, Elena; Pfister, Dominik; Johlke, Anna-Lena; Sinha, Ankit; Sankowski, Roman; Schick, Markus; Lewis, Richard; Dokalis, Nikolaos; Seubert, Bastian; Hoechst, Bastian; Inverso, Donato; Heide, Danijela; Zhang, Wenlong; Weihrich, Petra; Manske, Katrin; Wohlleber, Dirk; Anton, Martina; Hoellein, Alexander; Seleznik, Gitta; Bremer, Juliane; Bleul, Sabine; Augustin, Helmut G.; Scherer, Florian; Ködel, Uwe; Weber, Achim; Protzer, Ulrike; Foerster, Reinhold; Wirth, Thomas; Aguzzi, Adriano; Meissner, Felix; Prinz, Marco; Baumann, Bernd; Hoepken, Uta E.; Knolle, Percy A.; Baumgarten, Louisa von; Keller, Ulrich; Heikenwalder, Mathias (2019): Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention. In: Cancer Cell, Vol. 36, No. 3

Abstract

How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-KB-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.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1535-6108
• Language: English