Discussion
Our study may provide novel insights into LUAD progression related to the TME mechanism and new possibilities for improving adoptive immunotherapy.
Methods
Bioinformatic analysis was used to analyze TCGA data. RT-PCT, Western blot, luciferase assay and immunohistochemistry were used to detect the expression levels and bindings of genes and miRNA. ELISA and cytotoxic assay were used to evaluate CD8+ T cell function.
Results
In this study, bioinformatic analysis unveiled the miR-505-3p/NET1 pair as a CD8+ T-tumor-infiltrating lymphocyte (TIL) regulator. Then, we confirmed the bioinformatic results with LUAD patient samples, and NET1 was shown to be a direct target of miR-505-3p in a luciferase assay. Functional experiments demonstrated that miR-505-3p enhanced CD8+ T-TIL function, while NET1 impaired CD8+ T-TIL function and partly reversed the effects of miR-505-3p. The observed effects might be exerted via the regulation of immunosuppressive receptors in T cells.