MicroRNAs with Multiple Targets of Immune Checkpoints, as a Potential Sensitizer for Immune Checkpoint Inhibitors in Breast Cancer Treatment

SIMPLE SUMMARY: Based on the latest research progresses, application of immune checkpoint inhibitors (ICIs) has shown promise in treating breast cancer. Moreover, novel ICIs based combined therapy has been sought to further enhance the curative effect. This review brings up a whole new conception of combined strategy by adding miRNA therapy into immune checkpoint blockade (ICB), based on the fact that miRNAs targeting multiple immune checkpoint molecules are believed to enhance the efficacy of ICB by mimicking combination therapy. Potential miRNAs have been summarized in this study. We also discussed the potential side-effects and solutions of applying such method. To thoroughly evaluate the role of miRNAs with multiple immune checkpoint molecules to act as a novel additive therapy for ICB in cancer treatment in future study, may further improve the clinical benefit of cancer immunotherapy. ABSTRACT: Breast cancer is the most common cancer type and the leading cause of cancer-associated mortality in women worldwide. In recent years, immune checkpoint inhibitors (ICIs) have made significant progress in the treatment of breast cancer, yet there are still a considerable number of patients who are unable to gain lasting and ideal clinical benefits by immunotherapy alone, which leads to the development of a combination regimen as a novel research hotspot. Furthermore, one miRNA can target several checkpoint molecules, mimicking the therapeutic effect of a combined immune checkpoint blockade (ICB), which means that the miRNA therapy has been considered to increase the efficiency of ICIs. In this review, we summarized potential miRNA therapeutics candidates which can affect multiple targets of immune checkpoints in breast cancer with more therapeutic potential, and the obstacles to applying miRNA therapeutically through the analyses of the resources available from a drug target perspective. We also included the content of “too many targets for miRNA effect” (TMTME), combined with applying TargetScan database, to discuss adverse events. This review aims to ignite enthusiasm to explore the application of miRNAs with multiple targets of immune checkpoint molecules, in combination with ICIs for treating breast cancer.