Long Noncoding RNA lncNDEPD1 Regulates PD-1 Expression via miR-3619-5p in CD8 T Cells.

Therapies targeting programmed cell death protein 1 (PD-1) have gained great success in patients with multiple types of cancer. The regulatory mechanisms underlying PD-1 expression have been extensively explored. However, the impact of long noncoding RNAs on PD-1 expression remains elusive. In this study, we identified the Notch1/ axis, which plays a critical role in PD-1 expression in human CD8 T cells. RNA sequencing and quantitative reverse transcription PCR data showed that was upregulated in activated T cells, especially in PD-1 subsets. Fluorescence in situ hybridization demonstrated that was localized in the cytoplasm. A mechanistic study showed that could bind with miR-3619-5p and mRNA to prevent mRNA degradation and then upregulate PD-1 expression. A chromatin immunoprecipitation assay showed that Notch1 directly binds to the promoter of instead of Furthermore, chimeric Ag receptor T cells expressing -specific short hairpin RNAs were generated. Chimeric Ag receptor T cells with decreased expression showed enhanced tumoricidal effects when PD-L1 was present. Our work uncovered a new regulatory mechanism of PD-1 expression and thus provided a potential target to decrease PD-1 without affecting T cell function.