Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.683007
Keywords
primary central nervous system lymphoma (PCNSL); single cell sequencing; cellular heterogeneity; immune microenvironment; pathogenic and therapeutic; cell communication
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Funding
- Innovation Cultivation Fund of the Sixth Medical Center of PLA General Hospital
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Single-cell RNA sequencing of PCNSL tissue revealed diverse cell populations, with significant cellular interactions between B cells and other cells. Additionally, downregulation of gene expression and immune function of macrophages in PCNSL compared to normal tissue was observed, suggesting a potential target for PCNSL therapy.
Background Primary central nervous system lymphoma (PCNSL) is characterized by a lack of specificity and poor prognosis. Further understanding of the tumor heterogeneity and molecular phenotype of PCNSL is of great significance for improving the diagnosis and treatment of this disease. Methods To explore the distinct phenotypic states of PCNSL, transcriptome-wide single-cell RNA sequencing was performed on 34,851 PCNSL cells from patients. The cell types, heterogeneity, and gene subset enrichment of PCNSL were identified. A comparison of the PCNSL cells with 21,250 normal human fetal brain (nHFB) cells was further analyzed to reveal the differences between PCNSL and normal sample. Results Six cell populations were mainly identified in the PCNSL tissue, including four types of immune cells-B cell, T cell, macrophage and dendritic cell-and two types of stromal cells: oligodendrocyte and meningeal cell. There are significant cellular interactions between B cells and several other cells. Three subpopulations of B cells indicating diffident functions were identified, as well as a small number of plasma cells. Different subtypes of T cells and dendritic cells also showed significant heterogeneity. It should be noted that, compared with normal, the gene expression and immune function of macrophages in PCNSL were significantly downregulated, which may be another important feature of PCNSL in addition to B cell lesions and may be a potential target for PCNSL therapy.
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