RNA modifications in the tumor microenvironment: insights into the cancer-immunity cycle and beyond

Abstract

The chemical modification of biological molecules is a critical regulatory mechanism for controlling molecular functions. Although research has long focused on DNA and proteins, RNA modifications have recently attracted substantial interest with the advancement in detection technologies. In oncology, many studies have identified dysregulated RNA modifications including m6A, m1A, m5C, m7G, pseudouridylation and A to I editing, leading to disrupted downstream pathways. As the concept of the tumor microenvironment has gained prominence, studies have increasingly examined the role of RNA modifications in this context, focusing on interactions among cancer cells, immune cells, stromal cells, and other components. Here we review the RNA modifications in the tumor microenvironment through the perspective of the Cancer-Immunity Cycle. The extracellular RNA modifications including exosomes and influence of microbiome in RNA modifications are potential research questions. Additionally, RNA modifying enzymes including FTO, ALKBH5, METTL3, PUS7 are under investigation as potential biomarkers and targets for combination with immunotherapies. ADCs and mimetics of modified RNA could be potential novel drugs. This review discusses the regulatory roles of RNA modifications within the tumor microenvironment.

Keywords: Cancer-immunity cycle; Pseudouridylation; RNA modification; Tumor microenvironment; m6A.