089 Desmoglein 2 promotes tumor development through miR-146a/IRAK1/IL-8 signaling axis

The cadherin Dsg2 plays critical roles in cell growth and survival is up-regulated many cancers including skin head neck. We recently showed that down-regulates the tumor suppressor, miR-146a, up-regulates pro-inflammatory chemokine, IL-8. Furthermore, enhances small extracellular vesicle (sEV) release, which serve as a carrier of IL-8 on their surface potentially for receptor transactivation. In this study, bulk RNAseq analysis HNSCC biopsies from patients treated with PD-1 inhibitor, nivolumab, revealed was significantly higher HPV (+) compared to HPV(-) before treatment down-regulated response treatment. Visium spatial transcriptomic single confirmed Dsg2, IRAK1, are co-expressed malignant, aggressive cells. HPV(+) non-responders had levels plasma determined by ELISA, blood-borne sEV miR-146a lower non-responders, indicating miR-146a/Dsg2/IL-8 signaling axis may influence clinical trial outcome. To assess role SCC, we used XMIRXpress system overexpress facilitate loading into sEV. Treatment cells loaded decreased IRAK1 reduced proliferative capacity. Using xenograft model, lines expressing burden control. Overall, elevated favorable prognostic marker HNSCC, functions mechanistically its regulation