Study of Circulating MicroRNAs as biomarkers for guided Immunotherapy in Head and Neck carcinoma patients: A tool for personalized medicine

Background Head and neck squamous cell carcinomas (HNSCC) are solid tumors originating from the mucosa of the upper aerodigestive tract, pharynx, larynx, mouth, and nasal cavity. HNSCC is the sixth most common cancer worldwide characterized by metastatic evolution and poor prognosis. Immune checkpoint blockers (ICBs) for advanced HNSCC stages have been recently approved as standard therapy. Effectiveness of immunotherapy is heterogeneous and varies among patients and HNSCC types, which highlights the need to identify reliable biomarkers able to predict response to therapy. MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in the regulation of gene expression. They are detectable in cells and body fluids such as blood, where they are ideal candidates as non-invasive biomarkers. Aim Here, we investigated the miRNAs expression profiles as potential biomarker for guided immunotherapy in HNSCC patients. Methods Nanostring nCounter Human v3 miRNA expression assay (NanoString Technologies, Seattle, WA, USA) was used to determine the miRNAs expression profile from plasma samples of a discovery cohort of HNSCC patients treated at first line with immunotherapy and from a cohort of healthy controls. The analysis of raw miRNA data was performed using nSolver 4.0 Software (NanoString, Seattle, WA, USA). Before data normalization, nCounter data quality control (QC) was assessed. Results Nanostring profiling of 800 miRNAs resulted in a clear separation of patients and healthy controls. Differential expression analysis between Responder (R) and Non-responder (NR) patients to immunotherapy treatment allowed the identification of 21 miRNAs differentially expressed, of which 3 microRNAs upregulated and 18 microRNAs downregulated in NR. Conclusions Taken together, these data report a series of miRNAs that could be used as predictive biomarkers of response to immunotherapy treatment. Ongoing experiments are focused on the validation of the differentially expressed miRNAs in an independent patients’ cohort and in shedding light to their biological role.