Exosomal MicroRNA Levels Associated with Immune Checkpoint Inhibitor Therapy in Clear Cell Renal Cell Carcinoma

Abstract

Immunotherapy with immune checkpoint inhibitors (ICIs) has shown high efficiency in clear cell renal cell carcinoma (ccRCC) treatment. However, the response to therapy among patients varies greatly. Modern studies demonstrate the high potential of exosomal miRNAs as diagnostic and prognostic markers in oncopathology. This study aimed to evaluate exosomal miRNA expression profiles of miRNAs-144, -146a, -149, -126, and -155 in patients with clear cell renal cell carcinoma treated with immune checkpoint inhibitors. The study included 35 patients whose venous blood samples were taken before and after ICI therapy. Expression analysis was performed using real-time quantitative PCR. It was demonstrated that the level of microRNA-146a increased after therapy (median(IQR) 12.92(4.06–18.90)) compared with the level before it (median(IQR) 7.15(1.90–10.50); p-value = 0.006). On the contrary, microRNA-126 was reduced after therapy with immune checkpoint inhibitors (median(IQR) 0.85(0.55–1.03) vs. 0.48(0.15–0.68) before and after therapy, respectively; p-value = 0.0001). In addition, miRNA-146a expression was shown to be reduced in patients with a higher grade of immune-related adverse events (p-value = 0.020). The AUC value for the miRNA-146a and miRNA-126 combination was 0.752 (95% CI 0.585–0.918), with the sensitivity at 64.3% and the specificity at 78.9%. Thus, while it can be assumed that miRNA-146a and miRNA-126 can be used as predictors for ICI therapy effectiveness, additional in-depth studies are required.

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“…The work revealed that the expression levels of hsa-mir-92a-1-5p, hsa-mir-149-3p, and hsa-mir-424-3p were significantly abnormal in RCC patients so that they can be potentially used as biomarkers for RCC diagnosis. Exosomes have also been shown to be implicated in prognosis prediction and therapeutic response in RCC, as stated by Ivanova et al in their 2023 study [30]. The authors focused on exosomal venous blood miRNA expression profiles of miRNAs-144, -146a, -149, -126, and -155 in 35 patients with ccRCC treated with immune checkpoint inhibitors.…”

MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

“…The expression levels of exosomal miRNA-146a and miRNA-126 , which are associated with the regulation of immune responses, were examined in clear cell renal cell carcinoma (ccRCC) patients before and after PD-1 and PD-L1 therapy [ 184 ].…”

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“…Renal cell carcinoma (RCC) is one of the tumors with immune infiltration. The tumor microenvironment influences tumor biology and response to therapy, 85 and much evidence suggests that specific metabolic pathway activation plays a role in renal cancer angiogenesis, inflammatory response and modulation of immune infiltration. 86 Several studies have shown that activation of specific metabolic pathways may lead to the development of renal cell carcinoma.…”