miRNA重塑胰腺癌免疫微环境：作用机制与 治疗新策略
Remodeling the Pancreatic Cancer Immune Microenvironment by miRNA: Mechanisms and Novel Therapeutic Strategies
DOI: 10.12677/acm.2026.162476, PDF,    科研立项经费支持
作者: 王凯伦, 郭沛桐：黑龙江中医药大学第一临床医学院，黑龙江 哈尔滨；李 冀*：黑龙江中医药大学基础医学院，黑龙江 哈尔滨
关键词: 胰腺癌；miRNA；免疫微环境；免疫治疗；纳米递送；临床转化；Pancreatic Cancer； miRNA； Immune Microenvironment； Immunotherapy； Nanoparticle Delivery； Clinical Translation
摘要: 胰腺癌(PC)高度免疫抑制的微环境是其治疗失败的关键原因。微小RNA (miRNA)作为核心转录后调控因子，在塑造PC免疫微环境中扮演着枢纽角色。本文系统阐述了miRNA如何通过调控肿瘤细胞免疫原性(如靶向PD-L1)、浸润免疫细胞功能(如T细胞、巨噬细胞)以及癌相关成纤维细胞(CAFs)的活性，驱动免疫逃逸。在此基础上，深入评述了以miRNA为靶点的免疫治疗新策略，包括使用miRNA激动剂(如miR-34a、miR-194-5p)逆转抑制信号，以及应用抑制剂(如抗miR-21、抗miR-155)解除免疫刹车，并强调了纳米递送技术对于实现这些策略靶向递送的核心作用。最后，剖析了相关疗法临床转化的主要瓶颈。旨在为通过干预miRNA网络以重塑PC免疫微环境、提升免疫治疗疗效提供系统的理论依据和前沿视角。
Abstract: The highly immunosuppressive microenvironment is a key determinant of therapeutic failure in pancreatic cancer (PC). MicroRNAs (miRNAs), as crucial post-transcriptional regulators, play a pivotal role in sculpting the PC immune landscape. This review systematically elaborates on how miRNAs drive immune evasion through three core mechanisms: modulating tumor cell immunogenicity (e.g., targeting PD-L1), reprogramming the function of infiltrating immune cells (e.g., T cells, macrophages), and orchestrating the immunosuppressive activity of cancer-associated fibroblasts (CAFs). Building on this mechanistic foundation, we critically examine novel miRNA-targeted therapeutic strategies, including the use of miRNA agonists (e.g., miR-34a, miR-194-5p mimics) to restore immune-activating signals and inhibitors (e.g., anti-miR-21, anti-miR-155) to relieve immune suppression, highlighting the enabling role of nanotechnology for targeted delivery. Finally, we analyze the major bottlenecks in clinical translation and propose future directions. This review aims to provide the theoretical underpinnings and cutting-edge perspective on manipulating miRNA networks to remodel the PC immune microenvironment and enhance immunotherapy efficacy.
文章引用：王凯伦, 郭沛桐, 李冀. miRNA重塑胰腺癌免疫微环境：作用机制与 治疗新策略[J]. 临床医学进展, 2026, 16(2): 974-981. https://doi.org/10.12677/acm.2026.162476

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