Regulation of PD-L1 and PD-L2 Expression by Micrornas in Non-Small Cell Lung Cancer

Abstract

The 90's of the last century abounded in the discovery of immune checkpoints that means molecules present on the surface of immune system cells regulating its activity. The most important immune checkpoints include: PD-1 and its ligand - PD-L1 and PD-L2 molecules. Both ligands inhibit T cell activity through binding to PD-1 receptor on T cells. Today's immunotherapy is aimed at blocking the immune of checkpoints causing activation of T cell function. This is possible due to specific monoclonal antibodies, including nivolumab, pembrolizumab, atezolizumab, durvalumab and avelumab. The blocking of immunological molecules of immune control points, restores the natural anti-tumor activity of cytotoxic lymphocytes, leading to effective destruction of cancer cells. Previous studies have proved that many types of microRNAs participate in the regulation of the expression of PD-1, PD-L1 and PD-L2 molecules, including miR-200, -197, -33a, -34. The microRNA functions can be attributed to participation in the processes of differentiation, proliferation and apoptosis, migration, metabolism regulation and cellular response to stress. MicroRNAs affect the regulation of approximately 2/3 of all genes expression, mainly by blocking translation by joining with the protein complex and the 3'UTR end of mRNA. In each of the studies mentioned, the PD-L1 gene expression is closely correlated with the level of selected microRNAs, which has a huge impact on their functioning. Along with the combination of knowledge about microRNAs and the effectiveness of anti-PD-1 and anti-PD-L1 antibodies treatment of tumors may turn out to contribute in increasing the effectiveness of anticancer therapy.