New Era of Microrna: Low Blood Level of Tumor Suppressor Mir-5193 as a Target for Pd-L1 Immunotherapy in Esophageal Cancer

Background Recent studies have identified that low levels of some tumor suppressor microRNAs (miRNAs) in the blood contribute to tumor progression and poor outcomes in various cancers. However, no study has proved these miRNAs are associated with cancer immune mechanisms. In this study, we identified a novel tumor suppressor miRNA that targets PD-L1 and is significantly downregulated in the blood of esophageal squamous cell carcinoma (ESCC) patients. We also evaluated its potential for clinical application in ESCC. Methods From a systematic review of the NCBI and miRNA databases, four tumor suppressor miRNA candidates were selected (miR-5193, miR-4496, miR-651–3p, miR-802, miR-570-3p) that putatively target programmed cell death ligand 1 (PD-L1). Results Test-scale and large-scale analyses revealed that plasma levels of miR-5193 were significantly lower in ESCC patients than in healthy volunteers (HVs). Low plasma levels of miR-5193 were associated with advanced lymphatic invasion, tumor depth, and pathological stages, and were identified as an independent prognostic factor for poor outcomes. Overexpression of miR-5193 in ESCC cells suppressed PD-L1 on the surface of ESCC cells, even with IFN-γ stimulation. In the coculture model of tumor cells and T cells stimulated by anti-CD3/anti-CD28 beads, overexpression of miR-5193 increased the anti-tumor activity of T cells by suppressing PD-L1 expression. Conclusion Low blood levels of miR-5193 are associated with ESCC progression and poor outcomes and could be a target of nucleic acid immunotherapy in ESCC patients.