肿瘤相关成纤维细胞在胰腺导管腺癌中的研究进展

doi:10.3877/cma.j.issn.2095-3232.2026.01.020

胰腺导管腺癌（PDAC）是一种恶性程度极高且预后极差的消化道肿瘤，当前研究主要围绕其核心驱动基因突变（如KRAS/TP53）、以肿瘤相关成纤维细胞（CAFs）异常活化和免疫抑制为特征的致密纤维化微环境，以及化疗抵抗机制展开，前沿探索方向涵盖靶向治疗（如KRAS抑制剂）、免疫微环境调控、代谢通路干预及早期诊断标志物筛选。该文系统解析CAFs的生物学特性，涵盖其细胞起源、功能表型分类及分子异质性特征，并从调控恶性生物学行为、构建动态微环境网络、介导血管生成及免疫抑制等维度，全面阐述CAFs在PDAC进展中的核心作用。基于空间转录组与多重免疫荧光技术开发、表观遗传调控机制解析及联合治疗方案优化的研究路径，旨在为PDAC精准治疗提供新思路，改善患者预后。

关键词: 胰腺导管腺癌, 肿瘤相关成纤维细胞, 肿瘤微环境, 信号通路, 免疫调节

Pancreatic ductal adenocarcinoma (PDAC) is a type of digestive tract carcinoma with extremely high degree of malignancy and poor prognosis. At present, relevant research mainly focuses on the core driver gene mutation (such as KRAS/TP53), dense fibrotic microenvironment characterized by abnormal activation and immunosuppression of cancer-associated fibroblasts (CAFs), and the mechanism of chemotherapy resistance. The frontier exploration directions cover targeted therapy (such as KRAS inhibitors), immune microenvironment regulation, metabolic pathway intervention and screening of early diagnostic biomarkers. In this article, biological characteristics of CAFs were illustrated, including cell origin, functional phenotype classification and molecular heterogeneity. The key role of CAFs in the progression of PDAC was unraveled from the perspectives of regulating malignant biological behavior, constructing dynamic microenvironment network and mediating angiogenesis and immunosuppression, etc. Based on the development of spatial transcriptome and multiplex immunofluorescence imaging, analysis of epigenetic regulation mechanism and optimization of combined treatment regimens, this study was designed to provide novel ideas for precise treatment and improve clinical prognosis of PDAC patients.

Key words: Pancreatic ductal adenocarcinoma, Cancer-associated fibroblasts, Tumor microenvironment, Signaling pathways, Immune modulation

图1 PDAC微环境中CAFs发挥核心调控功能示意图注：PDAC为胰腺导管腺癌，CAFs为肿瘤相关成纤维细胞，ECM为细胞外基质，Tregs为调节性T细胞，TAMs为肿瘤相关性巨噬细胞

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Research progress in cancer-associated fibroblasts in pancreatic ductal adenocarcinoma

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Research progress in cancer-associated fibroblasts in pancreatic ductal adenocarcinoma