Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore 570020, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore 570020, India.
Semin Cell Dev Biol. 2022 Apr;124:99-113. doi: 10.1016/j.semcdb.2021.04.001. Epub 2021 Apr 15.
Chemoresistance is a major hindrance in cancer chemotherapies, a leading cause of tumor recurrence and cancer-related deaths. Cancer cells develop numerous strategies to elude immune attacks and are regulated by immunological factors. Cancer cells can alter the expression of several immune modulators to upregulate the activities of immune checkpoint pathways. Targeting the immune checkpoint inhibitors is a part of the cancer immunotherapy altered during carcinogenesis. These immune modulators have the capability to reprogram the tumor microenvironment, thereby change the efficacy of chemotherapeutics. In general, the sensitivity of drugs is reduced in the immunosuppressive tumor microenvironment, resulting in chemoresistance and tumor relapse. The regulation of microRNAs (miRNAs) is well established in cancer initiation, progression, and therapy. Intriguingly, miRNA affects cancer immune surveillance and immune response by targeting immune checkpoint inhibitors in the tumor microenvironment. miRNAs alter the gene expression at the post-transcriptional level, which modulates both innate and adaptive immune systems. Alteration of tumor immune microenvironment influences drug sensitivity towards cancer cells. Besides, the expression profile of immune-modulatory miRNAs can be used as a potential biomarker to predict the response and clinical outcomes in cancer immunotherapy and chemotherapy. Recent evidences have revealed that cancer-derived immune-modulatory miRNAs might be promising targets to counteract cancer immune escape, thereby increasing drug efficacy. In this review, we have compiled the role of miRNAs in overcoming the chemoresistance by modulating tumor microenvironment and discussed their preclinical and clinical implications.
化学耐药性是癌症化疗的主要障碍，也是肿瘤复发和癌症相关死亡的主要原因。癌细胞会采用多种策略来躲避免疫攻击，并受免疫因素的调节。癌细胞可以改变几种免疫调节剂的表达，上调免疫检查点途径的活性。靶向免疫检查点抑制剂是癌症发生过程中改变的癌症免疫疗法的一部分。这些免疫调节剂能够重新编程肿瘤微环境，从而改变化疗药物的疗效。一般来说，在免疫抑制性肿瘤微环境中，药物的敏感性降低，导致化学耐药性和肿瘤复发。miRNA 在癌症的发生、进展和治疗中的调控作用已经得到了很好的证实。有趣的是，miRNA 通过靶向肿瘤微环境中的免疫检查点抑制剂来影响癌症的免疫监视和免疫反应。miRNA 通过在转录后水平改变基因表达，调节固有和适应性免疫系统。肿瘤免疫微环境的改变会影响癌细胞对药物的敏感性。此外，免疫调节 miRNA 的表达谱可以作为预测癌症免疫治疗和化疗反应和临床结果的潜在生物标志物。最近的证据表明，癌症来源的免疫调节 miRNA 可能是对抗癌症免疫逃逸的有前途的靶点，从而提高药物疗效。在这篇综述中，我们总结了 miRNA 通过调节肿瘤微环境克服化学耐药性的作用，并讨论了它们的临床前和临床意义。
