{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Heming M"],"funding":["Westfälische Wilhelms-Universität Münster","Deutsche Forschungsgemeinschaft","Interdisciplinary Center for Clinical Research of the medical faculty of Münster"],"pagination":["109"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9509601"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(1)"],"pubmed_abstract":["<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>PCNSL-released cells were predominantly activated CD19<sup>+</sup>CD20<sup>+</sup>CD38<sup>+</sup>CD27<sup>+</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.<h4>Conclusions</h4>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."],"journal":["Genome medicine"],"pubmed_title":["Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma."],"pmcid":["PMC9509601"],"funding_grant_id":["FF-2016-10","ME4050/8-1","ME4050/13-1","ME4050/4-1","SEED/016/21","ME4050/12-1)","MzH3/020/20"],"pubmed_authors":["Wiendl H","Holling M","Thomas C","Wolbert J","Brokinkel B","Hailfinger S","Schulte-Mecklenbeck A","Li X","de Faria F","Grauer OM","Haessner S","Lu IN","Muther M","Stummer W","Heming M","Stoeckius M","Meyer Zu Horste G","Lenz G","Kerl K"],"additional_accession":[]},"is_claimable":false,"name":"Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma.","description":"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>PCNSL-released cells were predominantly activated CD19<sup>+</sup>CD20<sup>+</sup>CD38<sup>+</sup>CD27<sup>+</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.<h4>Conclusions</h4>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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-06-01T02:26:17.877Z","creation":"2025-04-05T13:31:04.354Z"},"accession":"S-EPMC9509601","cross_references":{"pubmed":["36153593"],"doi":["10.1186/s13073-022-01110-1"]}}