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. 2019 Sep 16;36(3):250-267.e9.
doi: 10.1016/j.ccell.2019.08.001.

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

Tracy O'Connor  1 , Xiaolan Zhou  2 , Jan Kosla  3 , Arlind Adili  4 , Maria Garcia Beccaria  5 , Elena Kotsiliti  3 , Dominik Pfister  3 , Anna-Lena Johlke  4 , Ankit Sinha  6 , Roman Sankowski  7 , Markus Schick  8 , Richard Lewis  8 , Nikolaos Dokalis  7 , Bastian Seubert  4 , Bastian Höchst  9 , Donato Inverso  10 , Danijela Heide  5 , Wenlong Zhang  11 , Petra Weihrich  12 , Katrin Manske  9 , Dirk Wohlleber  9 , Martina Anton  9 , Alexander Hoellein  8 , Gitta Seleznik  13 , Juliane Bremer  13 , Sabine Bleul  14 , Hellmut G Augustin  15 , Florian Scherer  14 , Uwe Koedel  11 , Achim Weber  16 , Ulrike Protzer  4 , Reinhold Förster  17 , Thomas Wirth  12 , Adriano Aguzzi  13 , Felix Meissner  6 , Marco Prinz  18 , Bernd Baumann  12 , Uta E Höpken  19 , Percy A Knolle  9 , Louisa von Baumgarten  11 , Ulrich Keller  20 , Mathias Heikenwalder  21
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Free article

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

Tracy O'Connor et al. Cancer Cell. .
Free article

Erratum in

  • Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention.
    O'Connor T, Zhou X, Kosla J, Adili A, Beccaria MG, Kotsiliti E, Pfister D, Johlke AL, Sinha A, Sankowski R, Schick M, Lewis R, Dokalis N, Seubert B, Höchst B, Inverso D, Heide D, Zhang W, Weihrich P, Manske K, Wohlleber D, Anton M, Hoellein A, Seleznik G, Bremer J, Bleul S, Augustin HG, Scherer F, Koedel U, Weber A, Protzer U, Förster R, Wirth T, Aguzzi A, Meissner F, Prinz M, Baumann B, Höpken UE, Knolle PA, von Baumgarten L, Keller U, Heikenwalder M. O'Connor T, et al. Cancer Cell. 2025 Jul 14;43(7):1377-1384. doi: 10.1016/j.ccell.2025.06.009. Epub 2025 Jul 3. Cancer Cell. 2025. PMID: 40614734 No abstract available.

Abstract

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.

Keywords: CCL19; CNSL; CXCL12; DLBCL; PCNSL; SCNSL; gliosis; lymphoma; metastasis; neuroinflammation.

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Comment in

  • How the brain retains lymphoma cells.
    Seton-Rogers S. Seton-Rogers S. Nat Rev Cancer. 2019 Nov;19(11):609. doi: 10.1038/s41568-019-0214-9. Nat Rev Cancer. 2019. PMID: 31570765 No abstract available.

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