胰腺癌微环境中巨噬细胞的作用机制及靶向治疗新进展

摘要

胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)是全球恶性程度最高、侵袭性最强的恶性肿瘤之一,多数患者确诊时已处于晚期。对于晚期胰腺癌,化疗仍为标准治疗手段,但其疗效常因严重不良反应与高度耐药性而受限。尽管近十年来免疫疗法发展迅速,但 PDAC 对免疫治疗的应答效果仍不理想,主要归因于肿瘤高度异质性、固有耐药性及显著的免疫抑制性肿瘤微环境。胰腺癌的肿瘤微环境是由多种细胞类型与分子组成的复杂调控网络,其中肿瘤细胞、免疫细胞、基质细胞和血管内皮细胞存在密切交互作用。肿瘤细胞通过分泌细胞因子和生长因子,招募并调控巨噬细胞、T 细胞、B 细胞、树突状细胞等免疫细胞,以及成纤维细胞、星形胶质细胞等基质细胞。这些细胞间的相互作用不仅驱动肿瘤的生长、侵袭与转移,更介导免疫逃逸与治疗耐药。从免疫抑制性微环境视角出发,PDAC 不良预后与肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs) 大量浸润密切相关,此类 TAMs 在肿瘤发生、进展及化疗耐药中发挥关键调控作用。本文基于现有研究进展,系统阐述巨噬细胞在 PDAC 进展中的交互作用机制及其生物学影响。

关键词

胰腺癌 / 肿瘤相关巨噬细胞 / 巨噬细胞极化 / 非编码 RNA / 外泌体 / 肿瘤内微生物

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基金资助

国家自然科学基金面上项目(82072754)