Kaur Maninder, Kaur Bhavneet, Konar Monidipa, Sharma Sadhna
Department of Biochemistry, PostGraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Biochemistry, PostGraduate Institute of Medical Education and Research, Chandigarh, India.
Adv Protein Chem Struct Biol. 2022;129:135-161. doi: 10.1016/bs.apcsb.2021.11.011. Epub 2022 Jan 11.
Immunotherapy is implemented as an important treatment strategy in various malignancies. In cancer, immunotherapy is employed for successful killing of tumor cells with high specificity and greater efficacy, with minimum side effects. Despite various available strategies, cellular immunotherapy including innate (NK cells, macrophages, dendritic cells) and adaptive (B cells and T cells) immune cells plays a critical role in tumor microenvironment. Since past few years, many drugs targeting immune checkpoint proteins including CTLA-4 and PD-1/PD-L1 have been investigated as immunotherapy approach against cancer but complete effectiveness still remains a question, as diverse mechanisms involved in tumorigenesis may result in the development of cancer cell resistance. Number of evidences have highlighted the significant role of non-coding RNAs (ncRNAs) in regulating multiple stages of cancer initiation, progression & immunity. ncRNAs comprises 98% human transcriptome and are basically considered as dark genome. Among ncRNAs, miRNAs and lncRNAs have been extensively studied in regulating diverse processes of cancer tumorigenesis. Upregulation of oncogenic and downregulation of tumor suppressive miRNAs/lncRNAs has been reported to facilitate the cancer progression and invasiveness. This chapter summarizes how an interplay between ncRNAs and immune cells in cancer pathogenesis can be therapeutically targeted to improve current treatment regimen. Strategies should be employed to improve the efficacy and reduce off-target effects of ncRNA based immunotherapy. Henceforth, combination of ncRNAs and available immunotherapy can be argued to enhance the efficacy of existing immunotherapeutic approaches against cancer to improve patient's survival.
免疫疗法是多种恶性肿瘤的重要治疗策略。在癌症治疗中，免疫疗法用于以高特异性、更高疗效和最小副作用成功杀死肿瘤细胞。尽管有多种可用策略，但包括先天免疫细胞（自然杀伤细胞、巨噬细胞、树突状细胞）和适应性免疫细胞（B细胞和T细胞）在内的细胞免疫疗法在肿瘤微环境中起着关键作用。在过去几年中，许多针对免疫检查点蛋白（包括细胞毒性T淋巴细胞相关蛋白4和程序性死亡受体1/程序性死亡配体1）的药物已作为抗癌免疫疗法进行研究，但完全有效性仍然是个问题，因为肿瘤发生涉及的多种机制可能导致癌细胞产生耐药性。大量证据突出了非编码RNA在调节癌症起始、进展和免疫的多个阶段中的重要作用。非编码RNA占人类转录组的98%，基本上被视为暗基因组。在非编码RNA中，微小RNA和长链非编码RNA在调节癌症肿瘤发生的各种过程中得到了广泛研究。据报道，致癌性微小RNA/长链非编码RNA的上调和肿瘤抑制性微小RNA/长链非编码RNA的下调促进了癌症进展和侵袭性。本章总结了如何在癌症发病机制中靶向非编码RNA与免疫细胞之间的相互作用，以改进当前的治疗方案。应采用策略提高基于非编码RNA的免疫疗法的疗效并减少脱靶效应。因此，可以认为将非编码RNA与现有免疫疗法相结合可提高现有抗癌免疫疗法的疗效，从而改善患者的生存率。
