Key Points
• Conclusion/Relevance: “Taken together, our findings firstly investigated systematic and comprehensive transcriptome characteristics of more than one thousand CSF-DLBCs at the single-cell level. We discovered that most CSF-DLBCs displayed immunoglobulin LCR [light chain restriction], active cell proliferation and energy metabolism properties, and inherent heterogeneity which were shown on the cell cycle state, CTA [cancer-testis antigens] expression, and classification by sc-GC B-cell signature. Despite a few patients, our study revealed biological insights of the intricate machinery responsible for CNS-DLBCL progression, and a larger validation cohort is required in the future.”
• Researchers performed scRNA-seq on 2,631 target cells from 7 patients and retained 2,114 cells (1,093 CSF-DLBCs) for later analysis. Use of scRNA-Seq allowed the researchers to directly compare the transcriptomes of pure normal B cells and CSF-DLBCs. Of note, gene expression in CSF-DLBCs was enriched in the cell proliferation and energy metabolism pathways vs normal cells, which is crucial for tumor growth and energy demand in the CSF-DLBCs.
• The Chinese researchers observed inherent heterogeneity of CSF-DLBCs, which were mostly exhibited in cell cycle state, cancer-testis antigen expression, and classification rooted in the single-cell germinal center B-cell signature. They also observed that the 16 upregulated genes in CSF-DLBCs vs the various normal B cells showed great potential in the homing effect of the CNS-DLBCL for the leptomeninges. The results shed light on the mechanisms and diagnostic direction of CNSL-DLBCL leptomeningeal involvement
• “The number of cells analyzed is relatively small for lack of various immune cells in the CSF tumor microenvironment,” the authors wrote. “In addition, although CSF-DLBCs serving as one type of circulating tumor cells could reflect the characteristics of CNSL from one aspect, they were in absence of information on tumor cells from the primary location. The gene expression of DLBCs at CSF might be substantially different from that of primary and leptomeningeal site which is worthy of further study.”