Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

Abstract

Tumor immunosuppression may assist the immune escape of cancer cells, which promotes tumor metastasis and resistance to chemo-radiotherapy. The therapeutic strategies against tumor immunosuppression mainly focus on blocking immune checkpoint receptors, enhancing T-cell recognition and neutralizing inhibitory molecules. Although immunotherapies based on these strategies have improved the clinical outcomes, immunological nonresponse and resistance are two barriers to tumor eradication. Therefore, there is an urgent need to identify new biomarkers for patient selection and therapeutic targets for the development of combination regimen with immunotherapy. Recent studies have reported that non-protein-coding modulators exhibit important functions in post-transcriptional gene regulation, which subsequently modulates multiple pathophysiological processes, including neoplastic transformation. Differentiated from microRNAs, long non-coding RNAs (lncRNAs) are reported to be involved in various processes of the immune response in the tumor microenvironment (TME) to promote tumor immunosuppression. Currently, studies on tumor immunity regulated by lncRNAs are mainly confined to certain types of cancer cells or stromal cells. Additionally, the majority of studies are focused on the events involved in T cells and myeloid-derived suppressor cells (MDSCs). Although the reported studies have indicated the significance of lncRNAs in immunotherapy, the lack of comprehensive studies prevents us from exploring useful lncRNAs. In the current review, we have summarized the roles of lncRNAs in tumor immune response, and highlighted major lncRNAs as potential biomarkers or therapeutic targets for clinical application of immunotherapy.

Keywords: biomarker; immune response; immunosuppression; long non-coding RNA; therapeutic target; tumor microenvironment.