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

O'Connor, Tracy; Zhou, Xiaolan; Kosla, Jan; Adili, Arlind; Garcia Beccaria, Maria; Kotsiliti, Elena; Pfister, Dominik; Johlke, Anna-Lena; Sinha, Ankit; Sankowski, Roman; Schick, Markus; Lewis, Richard; Dokalis, Nikolaos; Seubert, Bastian; Höchst, Bastian; Inverso, Donato; Heide, Danijela; Zhang, Wenlong; Weihrich, Petra; Manske, Katrin; Wohlleber, Dirk; Anton, Martina; Hoellein, Alexander; Seleznik, Gitta; Bremer, Juliane; Bleul, Sabine; Augustin, Hellmut G; Scherer, Florian; Koedel, Uwe; Weber, Achim; Protzer, Ulrike; Förster, Reinhold; Wirth, Thomas; Aguzzi, Adriano; Meissner, Felix; Prinz, Marco; Baumann, Bernd; Höpken, Uta E; Knolle, Percy A; von Baumgarten, Louisa; Keller, Ulrich; Heikenwälder, Mathias     «

O'Connor, Tracy; Zhou, Xiaolan; Kosla, Jan; Adili, Arlind; Garcia Beccaria, Maria; Kotsiliti, Elena; Pfister, Dominik; Johlke, Anna-Lena; Sinha, Ankit; Sankowski, Roman; Schick, Markus; Lewis, Richard; Dokalis, Nikolaos; Seubert, Bastian; Höchst, Bastian; Inverso, Donato; Heide, Danijela; Zhang, Wenlong; Weihrich, Petra; Manske, Katrin; Wohlleber, Dirk; Anton, Martina; Hoellein, Alexander; Seleznik, Gitta; Bremer, Juliane; Bleul, Sabine; Augustin, Hellmut G; Scherer, Florian; Koedel, Uwe; Weber,...     »

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.      «

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...     »