Long Non-Coding RNAs as Epigenetic Regulators of Immune Checkpoints in Cancer Immunity

Simple Summary Many non-coding RNAs are deregulated in cancer. In one of the most intriguing of their various roles, they control immune regulatory proteins, allowing tumor cells to evade the body's own defenses. In this work, we describe the mechanisms by which certain ncRNAs help tumor cells escape the immune response. In-depth insight into these mechanisms is required to further develop therapeutic strategies targeting immune checkpoints and improve the performance of cancer immunotherapy. In recent years, cancer treatment has undergone significant changes, predominantly in the shift towards immunotherapeutic strategies using immune checkpoint inhibitors. Despite the clinical efficacy of many of these inhibitors, the overall response rate remains modest, and immunotherapies for many cancers have proved ineffective, highlighting the importance of knowing the tumor microenvironment and heterogeneity of each malignancy in patients. Long non-coding RNAs (lncRNAs) have attracted increasing attention for their ability to control various biological processes by targeting different molecular pathways. Some lncRNAs have a regulatory role in immune checkpoints, suggesting they might be utilized as a target for immune checkpoint treatment. The focus of this review is to describe relevant lncRNAs and their targets and functions to understand key regulatory mechanisms that may contribute in regulating immune checkpoints. We also provide the state of the art on super-enhancers lncRNAs (selncRNAs) and circular RNAs (circRNAs), which have recently been reported as modulators of immune checkpoint molecules within the framework of human cancer. Other feasible mechanisms of interaction between lncRNAs and immune checkpoints are also reported, along with the use of miRNAs and circRNAs, in generating new tumor immune microenvironments, which can further help avoid tumor evasion.

Automated summary

Many non-coding RNAs play a role in cancer by controlling immune regulatory proteins, enabling tumor cells to evade the immune response. Understanding the mechanisms of these RNAs is crucial for developing therapeutic strategies and improving cancer immunotherapy. The focus of this review is to describe the role of long non-coding RNAs (lncRNAs) and their targets in regulating immune checkpoints.