Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma.
Genome Med
; 14(1): 109, 2022 Sep 24.
Article
en En
| MEDLINE
| ID: mdl-36153593
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
PCNSL-released cells were predominantly activated CD19+CD20+CD38+CD27+ 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.CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias del Sistema Nervioso Central
/
Linfoma
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Genome Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania