Cancer-derived non-coding RNAs endow tumor microenvironment with immunosuppressive properties.

Abstract

Non-coding RNAs (ncRNAs) have attracted extensive attention due to their vital roles in tumorigenesis and progression, especially in the immunotherapy resistance. Tumor immunotherapy resistance is a crucial factor hindering the efficacy of tumor treatments, which can be largely attributed to the immunosuppressive properties of tumor microenvironment. Current studies have revealed that cancer-derived ncRNAs are involved in the formation of tumor immunosuppressive microenvironment (TIME) through multiple ways. They not only promote the expression of immune checkpoint ligands (e.g., PD-L1, CD47, Gal-9, and CD276) on cancer cell surfaces, but also enhance the secretion of immunosuppressive cytokines (e.g., TGF-β, IL-6, IL-10, VEGF, and chemokines). Cancer-derived ncRNAs could also be transferred into surrounding immune-related cells through extracellular vesicles, thereby inhibiting the cytotoxicity of CD8⁺ T cells and NK cells, restraining the DC-mediated antigen presentation, inducing the immunosuppressive phenotype transformation of TAMs and CAFs, and enhancing the immunosuppressive functions of Tregs and MDSCs. Herein, we summarize the roles of cancer-derived ncRNAs in regulating TIME formation and further explore their potential applications as prognostic biomarkers and immunotherapeutic targets, which will help us to address the TIME-mediated immunotherapy resistance in the future. This article is categorized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.