Endoplasmic reticulum stressed HNSCC cell-derived exosomal miR-26a-5p promotes PD-L1 expression in macrophage through PTEN/AKT signaling pathway

Objective To investigate the impact of exosomal miRNAs derived from endoplasmic reticulum-stressed (ERS) head and neck squamous cell carcinoma (HNSCC) cells on macrophages. Methods This study was reviewed and approved by the Ethics Committee. The expression levels of ERS-associated proteins, including protein kinase R-like endoplasmic reticulum kinase (PERK) and glucose-regulated protein 78 (GRP78), in HNSCC tissues and para-tumor tissues were detected by Western blot (WB) and quantitative real-time PCR (RT-qPCR). HN4 human laryngeal squamous cell carcinoma cells were treated with 500 U/mL interferon-γ (IFN-γ) for 48 h to induce ER stress, and exosomes secreted by ER-stressed HN4 cells were collected and identified. The types of miRNAs in exosomes were identified through bioinformatics analysis, and the target genes of miRNAs were predicted. Macrophages were transfected with miRNA, co cultured with collected exosomes, and the expression of PTEN in macrophages was knocked down. The downstream signaling pathway regulated by exosomal miRNAs was studied by WB and RT-qPCR. Results Compared with that in para-tumor tissues, the expression level of ER stress-associated proteins in HNSCC tissues was increased (P