Role of miRNAs as epigenetic regulators of immune checkpoints in lung cancer immunity

The advent of immunotherapy in cancer has provided new avenues in the treatment of many malignancies at various stages. Specifically, immune checkpoint inhibitors (ICIs) have transformed the field of lung cancer treatment. However, since some tumors can evade the immune system, not all patients respond properly. Recent research has provided evidence showing how microRNAs (miRNAs) are involved in regulating many immune checkpoints. MiRNAs have demonstrated their ability to modulate immune evasion of tumor cells. Currently, reliable markers are being sought to predict the efficacy of immunotherapy in these types of cancers. Therefore, the association of serum miRNAs and the response of ICIs in lung cancer is under study. Many miRNA molecules and their corresponding target genes have been identified in the regulation of chemoresistance. Therefore, elucidating how these miRNAs control the function of immune checkpoints, as well as the effectiveness of therapies based on ICIs set the basis for the development of new biomarkers to predict treatment response to ICIs. This chapter delves into the molecular role of miRNAs interacting with ICs, such as PD-1 and PD-L1, and the clinical utility of miRNAs, such as miR-16, miR-146a, and miR-335, in predicting treatment response to ICI-based therapy in lung cancer. The aim is to provide a deep insight of the current landscape, serving as a cornerstone for further research.