Abstract
BackgroundPrimary 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.MethodsTo 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.ResultsSix 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.
Highlights
Primary central nervous system (CNS) lymphoma (PCNSL), defined as diffuse large B cell lymphoma (DLBCL) confined to the CNS, can occur in the setting of immunosuppression (HIV/ AIDS, post-transplant) or in immunocompetent individuals (1, 2)
The cell types were identified as B cell, T cell, macrophage, dendritic cell, oligodendrocyte, meningeal cell, excitatory neuron (EN), interneuron (IN), radial glia (RG), inhibitory neuronal progenitor cell (INP), excitatory neuronal progenitor (ENP), astrocyte, and oligodendrocyte progenitor cell (OPC) (Figure 1A and Table 1)
We mapped the immune microenvironment of PCNSL and identified the cellular markers and functional signals of immune cells such as B cells, macrophages, and dendritic cells in PCNSL, which provided a partial basis for guiding the precise treatment of PCNSL
Summary
Primary central nervous system (CNS) lymphoma (PCNSL), defined as diffuse large B cell lymphoma (DLBCL) confined to the CNS, can occur in the setting of immunosuppression (HIV/ AIDS, post-transplant) or in immunocompetent individuals (1, 2). The incidence of PCNSL accounting for 2% to 3% of all CNS neoplasms (3) has reportedly increased in the immunocompetent population (4). Incidence of PCNSL is recently increasing in the elderly (5). It is not possible to morphologically distinguish PCNSL and peripheral DLBCL. This non-Hodgkin aggressive Bcell lymphoma is distinguished from extra-cerebral DLBCL by its poorer prognosis. 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
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