Gene expression profile at single cell level of cerebrospinal fluid (CSF) cells from lung adenocarcinoma leptomeningeal metastases patients (LUAD LM)

Nevertheless, the cerebrospinal fluid (CSF) profile of LUAD-LM patients remains poorly characterized and reliable CSF diagnostic biomarkers for LUAD-LM have yet to be established. Using single-cell RNA sequencing data of CSF cells from six LUAD-LM patients, we drew a systematic transcriptomic atlas of the CSF cellular landscape.

Our analysis revealed that LUAD-LM reprograms CSF into an immunosuppressive state, marked by the emergence of pro-tumoral LGMN-SELENOPhigh macrophages and proliferating CSF circulating tumor cells (CSF-CTC). Cell-cell communication analysis showed that CSF-CTC reinforces immunosuppression by co-inhibitory checkpoint axis NECTIN2_TIGIT axis with the CD8+T/NK cells, and via CD47_SIRPA axis with antigen-presenting cells. Furthermore, we identified the single-cell transcriptomic difference between CSF-CTC and tumor cells of parenchymal brain metastases (PBM).