Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
Int Immunopharmacol. 2024 Nov 15;141:112967. doi: 10.1016/j.intimp.2024.112967. Epub 2024 Aug 23.
Tumor cells engage with the immune system in a complex manner, utilizing evasion and adaptability mechanisms. The development of cancer and resistance to treatment relies on the ability of immune cells to adjust their phenotype and function in response to cues from the tumor microenvironment, known as immunological cell plasticity. This study delves into the role of long non-coding RNAs (lncRNAs) in enhancing immune cell flexibility in cancer, focusing on their regulatory actions in the tumor microenvironment and potential therapeutic implications. Through a comprehensive review of existing literature, the study analyzes the impact of lncRNAs on macrophages, T-cells, and MDSCs, as well as the influence of cytokines and growth factors like TNF, IL-6, HGF, and TGFβ on immunological cell plasticity and tumor immunoediting. LncRNAs exert a strong influence on immune cell plasticity through mechanisms such as transcriptional regulation, post-transcriptional modifications, and chromatin remodeling. These RNA molecules intricately modulate gene expression networks, acting as scaffolding, decoys, guides, and sponges. Moreover, both direct cell-cell interactions and soluble chemicals in the tumor microenvironment contribute to enhancing immune cell activation and survival. Understanding the influence of lncRNAs on immune cell flexibility sheds light on the biological pathways of immune evasion and cancer progression. Targeting long non-coding RNAs holds promise for amplifying anti-tumor immunity and overcoming drug resistance in cancer treatment. However, further research is necessary to determine the therapeutic potential of manipulating lncRNAs in the tumor microenvironment.
肿瘤细胞以复杂的方式与免疫系统相互作用,利用逃避和适应性机制。癌症的发展和治疗耐药性依赖于免疫细胞根据肿瘤微环境中的信号调整其表型和功能的能力,这被称为免疫细胞可塑性。本研究探讨了长非编码 RNA(lncRNA)在增强癌症中免疫细胞灵活性方面的作用,重点关注它们在肿瘤微环境中的调节作用及其潜在的治疗意义。通过对现有文献的全面回顾,该研究分析了 lncRNA 对巨噬细胞、T 细胞和 MDSC 的影响,以及细胞因子和生长因子(如 TNF、IL-6、HGF 和 TGFβ)对免疫细胞可塑性和肿瘤免疫编辑的影响。lncRNA 通过转录调节、转录后修饰和染色质重塑等机制对免疫细胞可塑性产生强烈影响。这些 RNA 分子错综复杂地调节基因表达网络,充当支架、诱饵、向导和海绵。此外,肿瘤微环境中的直接细胞-细胞相互作用和可溶性化学物质都有助于增强免疫细胞的激活和存活。了解 lncRNA 对免疫细胞灵活性的影响揭示了免疫逃避和癌症进展的生物学途径。靶向长非编码 RNA 有望增强抗肿瘤免疫并克服癌症治疗中的耐药性。然而,需要进一步研究来确定在肿瘤微环境中操纵 lncRNA 的治疗潜力。