Exosomal miRNA-146a and miRNA-424 as Possible Predictors of Immune Checkpoint Inhibitors Therapy Response in Clear Cell Renal Cell Carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is a malignant kidney tumour with a poor prognosis and difficult to treat. Despite significant advances in the treatment of ccRCC, immune checkpoint inhibitors (ICI) still have limited therapeutic efficacy. A growing number of investigations has demonstrated that exosomal miRNAs are key modulators of tumour signaling and determinants of the tumour microenvironment. Disruption of miRNA regulation may affect ccRCC immunogenicity and response to ICI therapy, making them attractive for use as prognostic molecular genetic biomarkers. We evaluated exosomal miRNAs (miRNA-424, -146a, -503, -144) expression levels before and after ICI therapy in plasma samples obtained from 42 ccRCC patients. Expression analysis was performed using real-time PCR method. The results showed that the expression levels of miRNA-424 and miRNA-146a were upregulated after ICI therapy treatment (miRNA-424 = Mean ± SEM 1.202 ± 0.15 and miRNA-146a = 12.22 ± 1.45) compared expression levels before therapy (miRNA-424 = Mean ± SEM 0.63 ± 0.17; p-value = 0.03 and miRNA-146a = 7.03 ± 0.90; p-value = 0.006). miRNA-424 and miRNA-146a can be used to create a panel of molecular markers for evaluating the effectiveness of immune checkpoint inhibitors therapy. Even though the results are preliminary and requires further studying on a larger cohorts, it further increases the interest in using miRNAs, as additional ICI therapeutic markers capable of modulating immune tolerance.