Endogenous and tumour-derived microRNAs regulate cross-presentation in dendritic cells and consequently cytotoxic T...

Dendritic cells (DCs) are potent antigen presenting cells (APCs). They are also specialized in the induction of cytotoxic T lymphocyte mediated responses against extracellular antigens, including tumour-specific antigens, by presenting peptide-Major Histocompatibility Complex (MHC) I complexes to naïve CD8⁺ T cells in lymphoid tissues, a process called cross-presentation. Emerging evidence suggests that the efficiency of cross-presentation can be influenced by a unique set of microRNAs (miRNAs). Some are differentially expressed in the course of morphological and functional development of DCs while tumorigenic miRNAs (onco-miRs) can be delivered to and inserted into DCs via exosomes. The latter reprogram the miRNA repertoire of DCs, transforming them from effective APCs to negative modulators of immunity, ultimately aiding cancers to evade host immunity. On the other hand, endogenous microRNAs can influence cross-presentation either positively or negatively. In this review, we discuss the possible mechanisms by which specific miRNAs influence cross-presentation as well as the viability of manipulating the expression of miRNAs that regulate DC cross-presentation as a potential cancer immunotherapy intervention.