Non-coding RNAs in cancer immunotherapy: A solution to overcome immune resistance?

With the rapid advancement in immunotherapy, cancer immune resistance has become more evident, which demands new treatment approaches to achieve greater efficacy. Non-coding RNAs (ncRNAs) are a heterogeneous group of RNAs that are not translated to proteins but instead regulate different stages of gene expression. Recent studies have increasingly supported the critical role of ncRNAs in immune cell-cancer cell cross-talk, and numerous ncRNAs have been implicated in the immune evasion of cancer cells. Cancer cells take advantage of ncRNAs to modulate several signaling pathways and upregulate the expression of immune checkpoints and anti-inflammatory mediators, thereby dampening the anti-tumor response of M1 macrophages, dendritic cells, cytotoxic T cells, and natural killer cells or potentiating the immunosuppressive properties of M2 macrophages, regulatory T cells, and myeloid-derived suppressive cells. Upregulation of immunosuppressive ncRNAs or downregulation of immunogenic ncNRAs is a major driver of resistance to immune checkpoint inhibitors, cancer vaccines, and other means of cancer immunotherapy, making ncRNAs ideal targets for treatment. In addition, ncRNAs released by cancer cells have been demonstrated to possess prognostic values for patients who undergo cancer immunotherapy. Future clinical trials are urged to consider the potential of ncRNAs in cancer immunotherapy.