• Medientyp: E-Artikel
  • Titel: Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma
  • Beteiligte: Heming, Michael; Haessner, Svea; Wolbert, Jolien; Lu, I-Na; Li, Xiaolin; Brokinkel, Benjamin; Müther, Michael; Holling, Markus; Stummer, Walter; Thomas, Christian; Schulte-Mecklenbeck, Andreas; de Faria, Flavia; Stoeckius, Marlon; Hailfinger, Stephan; Lenz, Georg; Kerl, Kornelius; Wiendl, Heinz; Meyer zu Hörste, Gerd; Grauer, Oliver M.
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Genome Medicine
  • Sprache: Englisch
  • DOI: 10.1186/s13073-022-01110-1
  • ISSN: 1756-994X
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Primary central nervous system lymphoma (PCNSL) is a rare lymphoma of the central nervous system, usually of diffuse large B cell phenotype. Stereotactic biopsy followed by histopathology is the diagnostic standard. However, limited material is available from CNS biopsies, thus impeding an in-depth characterization of PCNSL.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We performed flow cytometry, single-cell RNA sequencing, and B cell receptor sequencing of PCNSL cells released from biopsy material, blood, and cerebrospinal fluid (CSF), and spatial transcriptomics of biopsy samples.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>PCNSL-released cells were predominantly activated CD19<jats:sup>+</jats:sup>CD20<jats:sup>+</jats:sup>CD38<jats:sup>+</jats:sup>CD27<jats:sup>+</jats:sup> B cells. In single-cell RNA sequencing, PCNSL cells were transcriptionally heterogeneous, forming multiple malignant B cell clusters. Hyperexpanded B cell clones were shared between biopsy- and CSF- but not blood-derived cells. T cells in the tumor microenvironment upregulated immune checkpoint molecules, thereby recognizing immune evasion signals from PCNSL cells. Spatial transcriptomics revealed heterogeneous spatial organization of malignant B cell clusters, mirroring their transcriptional heterogeneity across patients, and pronounced expression of T cell exhaustion markers, co-localizing with a highly malignant B cell cluster.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Malignant B cells in PCNSL show transcriptional and spatial intratumor heterogeneity. T cell exhaustion is frequent in the PCNSL microenvironment, co-localizes with malignant cells, and highlights the potential of personalized treatments.</jats:p> </jats:sec>
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