德国慕尼黑工业大学Mathias Heikenwalder、Tracy O'Connor等研究人员合作取得一项新成果。他们发现年龄相关性神经胶质增生通过CCL19介导的肿瘤细胞驻留促进中枢神经系统淋巴瘤（CNSL）。这一研究成果2019年9月16日发表在《癌细胞》上。

研究人员发现NF-κB诱导的神经胶质增生在免疫活性小鼠中促进CNSL。胶质增生使细胞粘附分子升高，这增加了脑中的淋巴瘤细胞（LC），但不足以产生CNSL。胶质细胞来源的CCL19是胶质细胞诱导的CNSL所必需的。从LC中敲除小鼠CCL19或敲除LC中的CCR7阻止了CNSL的发展。双光子显微镜显示LC瞬时进入正常的脑实质。星形胶质细胞CCL19增强了LC在CNS实质中的停留，从而促进了CNSL的形成。与年轻的野生型小鼠相比，老年的、胶质增生的野生型小鼠更容易形成CNSL，并且在人胶质增生和CNSL中观察到星形胶质细胞的CCL19。 因此，CCL19-CCR7相互作用可能是CNSL年龄相关风险增加的基础。

据介绍，LC在向CNSL发展过程中如何侵入大脑尚不清楚。

附：英文原文

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

Author: Tracy OConnor, 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 Hchst, Donato Inverso, Danijela Heide, Wenlong Zhang, Petra Weihrich, Katrin Manske, Dirk Wohlleber, Martina Anton, Alexander Hoellein, Gitta Seleznik, Juliane Bremer, Sabine Bleul, Hellmut G. Augustin, Florian Scherer, Uwe Koedel, Achim Weber, Ulrike Protzer, Reinhold Frster, Thomas Wirth, Adriano Aguzzi, Felix Meissner, Marco Prinz, Bernd Baumann, Uta E. Hpken, Percy A. Knolle, Louisa von Baumgarten, Ulrich Keller, Mathias Heikenwalder

Issue&Volume::Volume 36 Issue 3

Summary: 

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.

DOI: 10.1016/j.ccell.2019.08.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30369-1