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

OConnor 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; Koedel Uwe; Weber Achim; Protzer Ulrike; Foerster Reinhold; Wirth Thomas; Aguzzi Adriano; Meissner Felix; Prinz Marco; Baumann Bernd; Hoepken Uta E.; Knolle Percy A.; von Baumgarten Louisa; Keller Ulrich; Heikenwalder Mathias

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

机译：通过CCL19介导的肿瘤细胞保留促进中枢神经系统淋巴瘤的年龄相关的渗透率

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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.

机译：淋巴瘤细胞（LCS）如何在中枢神经系统淋巴瘤（CNSL）的发育过程中侵入大脑（CNSL）尚不清楚。我们发现NF-KB诱导的神经胶质症促进了免疫活性小鼠中的CNSL。脊髓亮升高的细胞粘附分子，增加了脑中的LCs但不足以诱导CNSL。神经细胞衍生的CCL19是针尖诱导的CNSL所必需的。从LCS废除CNSL发育中删除小鼠或CCR7中的CCL19。双光子显微镜显示LCS瞬间进入正常的脑薄壁症。星形胶质细胞CCL19增强了实质的CNS保留LCS，从而促进CNSL形成。老年人，嗜菌野生型小鼠比年轻野生型小鼠更容易形成CNSL，并且在人类神经胶质病和CNSL中观察到星形胶质细胞CCL19。因此，CCL19-CCR7相互作用可能提高CNSL的年龄相关的风险。

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《Cancer Cell》 |2019年第3期|共27页
作者
OConnor 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; Koedel Uwe; Weber Achim; Protzer Ulrike; Foerster Reinhold; Wirth Thomas; Aguzzi Adriano; Meissner Felix; Prinz Marco; Baumann Bernd; Hoepken Uta E.; Knolle Percy A.; von Baumgarten Louisa; Keller Ulrich; Heikenwalder Mathias;
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作者单位

Tech Univ Munich Inst Virol D-81675 Munich Germany;

Ludwig Maximilians Univ Hosp Munich Dept Neurol D-81377 Munich Germany;

Tech Univ Munich Inst Virol D-81675 Munich Germany;

Tech Univ Munich Inst Virol D-81675 Munich Germany;

German Canc Res Ctr Div Chron Inflammat &

Canc Neuenheimer Feld 242 D-69120 Heidelberg Germany;

Tech Univ Munich Inst Virol D-81675 Munich Germany;

Tech Univ Munich Inst Virol D-81675 Munich Germany;

Tech Univ Munich Inst Virol D-81675 Munich Germany;

Max Planck Inst Biochem Expt Syst Immunol Munich Germany;

Univ Freiburg Med Fac Inst Neuropathol D-79085 Freiburg Germany;

Tech Univ Munich Med Dept 3 D-81675 Munich Germany;

Tech Univ Munich Med Dept 3 D-81675 Munich Germany;

Univ Freiburg Med Fac Inst Neuropathol D-79085 Freiburg Germany;

Tech Univ Munich Inst Virol D-81675 Munich Germany;

Tech Univ Munich Inst Mol Immunol &

Expt Oncol Ismaningerstr 22 D-81675 Munich Germany;

German Canc Res Ctr Heidelberg DKFZ ZMBH Alliance Div Vasc Oncol &

Metastasis D-69120 Heidelberg;

German Canc Res Ctr Div Chron Inflammat &

Canc Neuenheimer Feld 242 D-69120 Heidelberg Germany;

Ludwig Maximilians Univ Hosp Munich Dept Neurol D-81377 Munich Germany;

Univ Ulm Inst Physiol Chem D-89081 Ulm Germany;

Tech Univ Munich Inst Mol Immunol &

Expt Oncol Ismaningerstr 22 D-81675 Munich Germany;

Tech Univ Munich Inst Mol Immunol &

Expt Oncol Ismaningerstr 22 D-81675 Munich Germany;

Tech Univ Munich Inst Mol Immunol &

Expt Oncol Ismaningerstr 22 D-81675 Munich Germany;

Tech Univ Munich Med Dept 3 D-81675 Munich Germany;

Univ Hosp Zurich Inst Neuropathol CH-8091 Zurich Switzerland;

Univ Hosp Zurich Inst Neuropathol CH-8091 Zurich Switzerland;

Albert Ludwigs Univ Med Ctr Freiburg Univ Dept Hematol Oncol &

Stem Cell Transplantat D-79106;

German Canc Res Ctr Heidelberg DKFZ ZMBH Alliance Div Vasc Oncol &

Metastasis D-69120 Heidelberg;

Albert Ludwigs Univ Med Ctr Freiburg Univ Dept Hematol Oncol &

Stem Cell Transplantat D-79106;

Ludwig Maximilians Univ Hosp Munich Dept Neurol D-81377 Munich Germany;

Univ Hosp Zurich Dept Pathol &

Mol Pathol CH-8091 Zurich Switzerland;

Tech Univ Munich Inst Virol D-81675 Munich Germany;

Hannover Med Sch Inst Immunol D-30625 Hannover Germany;

Univ Ulm Inst Physiol Chem D-89081 Ulm Germany;

Univ Hosp Zurich Inst Neuropathol CH-8091 Zurich Switzerland;

Max Planck Inst Biochem Expt Syst Immunol Munich Germany;

Univ Freiburg Med Fac Inst Neuropathol D-79085 Freiburg Germany;

Univ Ulm Inst Physiol Chem D-89081 Ulm Germany;

Max Delbruck Ctr Mol Med D-13092 Berlin Germany;

Tech Univ Munich Inst Mol Immunol &

Expt Oncol Ismaningerstr 22 D-81675 Munich Germany;

Ludwig Maximilians Univ Hosp Munich Dept Neurol D-81377 Munich Germany;

Tech Univ Munich Med Dept 3 D-81675 Munich Germany;

Tech Univ Munich Inst Virol D-81675 Munich Germany;

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正文语种 eng
中图分类肿瘤学;
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1. Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention [J] . OConnor Tracy, Zhou Xiaolan, Kosla Jan, Cancer Cell . 2019,第3期

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2. Relapse and Outcome Patterns of Patients With Central Nervous System Mixed Malignant Germ Cell Tumors Treated Without Irradiation: Findings From the Third International Central Nervous System (CNS) Germ Cell Tumor (GCT) Study [J] . Pruitt Rachel, DaSilva Nasjla S., Cappellano Andrea, Pediatric blood & cancer . 2015,第11期

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4. Mutational profile of Diffuse Large B-cell Lymphoma with central nervous system relapse: analysis of CBioPortal for Cancer Genomics database [C] . Elena Voropaeva, Olga Beresina, Tatyana Pospelova, Conference on Cognitive Sciences, Genomics and Bioinformatics . 2020

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5. Towards functional regeneration of the central nervous system: Glial calcium signaling in reactive gliosis and the therapeutic potential of bone marrow -derived mesenchymal stem cells for retinal degenerative diseases. [D] . Yu, Diana Xuan. 2008

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6. Central nervous system recurrence of systemic lymphoma in the era of stem cell transplantation – an International Primary Central Nervous System Lymphoma Study Group project [O] . Jacoline E. Bromberg, Jeanette K. Doorduijn, Gerald Illerhaus, 2013

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

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