miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy

Immunotherapy is presently one of the most promising areas of investigation and developmentfor the treatment of cancer. While immune checkpoint-blocking monoclonal antibodies andchimeric antigen receptor (CAR) T-cell-based therapy have recently provided in some cases valuabletherapeutic options, the goal of cure has not yet been achieved for most malignancies and moreefforts are urgently needed. Noncoding RNAs (ncRNA), including microRNAs (miRNAs) and longnoncoding RNAs (lncRNAs), regulate several biological processes via selective targeting of crucialmolecular signaling pathways. Recently, the key roles of miRNA and lncRNAs as regulators ofthe immune-response in cancer have progressively emerged, since they may act (i) by shaping theintrinsic tumor cell and microenvironment (TME) properties; (ii) by regulating angiogenesis, immuneescape,epithelial-to-mesenchymal transition, invasion, and drug resistance; and (iii) by acting aspotential biomarkers for prognostic assessment and prediction of response to immunotherapy. In thisreview, we provide an overview on the role of ncRNAs in modulating the immune response and theTME. We discuss the potential use of ncRNAs as potential biomarkers or as targets for developmentor clinical translation of new therapeutics. Finally, we discuss the potential combinatory approachesbased on ncRNA targeting agents and tumor immune-checkpoint inhibitor antibodies or CAR-T forthe experimental treatment of human cancer.