Data from Clinical importance of the lncRNA NEAT1 in cancer patients treated with immune checkpoint inhibitors.

AbstractPurpose: Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint are powerful tools to improve the survival of cancer patients. Understanding the molecular basis of clinical response to these treatments is critical to identify patients who can benefit from this immunotherapy. In this study, we investigated long non-coding RNA (lncRNA) expression in cancer patients treated with anti-PD-1/PD-L1 immunotherapy. Experimental design: LncRNA expression profile was analyzed in one cohort of melanoma patients and two independent cohorts of patients with glioblastoma (GBM) undergoing anti-PD-1/PD-L1 immunotherapy. Single-cell RNA-sequencing analyses were performed to evaluate lncRNA expression in tumor cells and tumor-infiltrating immune cells. Results:We identified the lncRNA NEAT1 as commonly upregulated between melanoma patients with complete therapeutic response and GBM patients with longer survival following anti-PD-1/PD-L1 treatment. Gene set enrichment analyses revealed that NEAT1 expression was strongly associated with the interferon-gamma pathways, along with downregulation of cell-cycle-related genes. Single-cell RNA-sequencing analyses revealed NEAT1 expression across multiple cell types within the GBM microenvironment, including tumor cells, macrophages, and T cells. High NEAT1 expression levels in tumor cells correlated with increased infiltrating macrophages and microglia. In these tumor-infiltrating myeloid cells, we found that NEAT1 expression was linked to enrichment in TNF alpha/NFKB signaling pathway genes. Silencing NEAT1 suppressed M1 macrophage polarization and reduced the expression of TNF alpha and other inflammatory cytokines. Conclusions: These findings suggest an association between NEAT1 expression and patient response to anti-PD-1/PD-L1 therapy in melanoma and GBM and have important implications for the role of lncRNAs in the tumor microenvironment.