Single-cell transcriptome analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

Abstract

Summary Diffuse large B cells in the cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of central nervous system lymphoma (CNSL) leptomeningeal involvement. To explore the phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of more than one thousand CSF-DLBCs from six patients with CNSL diffuse large B-cell lymphoma (DLBCL) using Smart-seq2 single-cell RNA sequencing. CSF-DLBCs were defined based on abundant expression of B-cell markers, the active cell proliferation and energy metabolism properties, and immunoglobulin light chain restriction. We identified inherent heterogeneity of CSF-DLBCs, which were mainly manifested in cell cycle state, cancer-testis antigen expression, and classification based on single-cell germinal center B-cell signature. In addition, the 16 upregulated genes in CSF-DLBCs compared to various normal B cells showed great possibility in the homing effect of the CNS-DLBCL for the leptomeninges. Our results will provide insight into the mechanism research and diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases

“…BC CSF‐CTCs had great heterogeneity shown on the cell‐cycle state and CTAs expression (Figure 5B,C), same as LC CSF‐CTCs 3 and CSF‐DLBCs 4 . CSF‐CTCs in basal‐like subtype, which always has higher probability of metastases and worse prognosis than other subtypes, showed highest proliferation ability (Figure 5A,B).…”

“…Previous studies have shown the CTAs characteristics of CSF malignant cells of LC 3 and central nervous system lymphoma. 4 Here, we focused on CTAs expression ( http://www.cta.lncc.br/modelo.php ) in the five subtype‐specific CSF‐CTCs. BC CSF‐CTCs had higher expression of 11 CTAs (Figure 5C , Table S6 ; PCT in CSF‐CTCs > 0.05), compared to normal breast epithelial cells of basal clusters and luminal clusters from three samples (GSE113196, Normal sample 4–6, N4–N6).…”

“…Previous studies have shown the CTAs characteristics of CSF malignant cells of LC 3 and central nervous system lymphoma 4 . Here, we focused on CTAs expression (http://www.cta.lncc.br/modelo.php) in the five subtype‐specific CSF‐CTCs.…”

“…BC CSF‐CTCs had great heterogeneity shown on the cell‐cycle state and CTAs expression (Figure 5B,C ), same as LC CSF‐CTCs 3 and CSF‐DLBCs. 4 CSF‐CTCs in basal‐like subtype, which always has higher probability of metastases and worse prognosis than other subtypes, showed highest proliferation ability (Figure 5A,B ). The CTAs expression were various in the five subtype‐specific CSF‐CTCs, and the CTA PRAME restricted to CSF‐CTCs are the potential therapeutic target (Figure 5C,D , Table S6 ).…”

“…Single-cell RNA sequencing (scRNA-seq) technology make us available to obtain the single-cell transcriptome data of CSF cells. For instance, scRNA-seq methods have fuelled the investigations of CSF-CTCs of LC 3 and central nervous system lymphoma, 4 and emphasised on the CSF microenvironment of HIV infection, 5 alzheimer's disease, 6 multiple sclerosis 7 and LM. 8 In this study, we intended to analyse the characteristics of CSF tumour microenvironment (TME) of LM patients.…”