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