肠促胰岛素和胰高血糖素对肿瘤微环境的调节：代谢和免疫机制（综述）
Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).
摘要(中文译文)
胰高血糖素样肽-1受体激动剂（GLP-1RAs）及靶向葡萄糖依赖性促胰岛素多肽（GIP）的疗法已证明在2型糖尿病（T2D）和肥胖症治疗中具有疗效。GLP-1和GIP统称为肠促胰岛素。T2D/肥胖与癌症风险之间强有力的流行病学关联提示，GLP-1和GIP可能在肿瘤代谢中发挥重要作用。肠促胰岛素激素及反向调节激素胰高血糖素（GCG）对肿瘤生物学的影响，可能对理解肿瘤微环境调控及指导癌症治疗具有重要意义。本综述总结了这些激素影响肿瘤微环境的机制。除肠促胰岛素和GCG的基础生物学外，本综述详细阐述了GLP-1RAs如何调节免疫细胞功能，包括T细胞、中性粒细胞、自然杀伤细胞和巨噬细胞的功能，以促进抗肿瘤免疫微环境。此外，本综述探讨了其在肿瘤代谢重编程中的作用，影响肿瘤细胞周期进程、细胞外基质重塑和线粒体功能。尽管临床前和临床数据提示GLP-1RAs可降低某些肥胖相关癌症类型（如胰腺癌和肝癌）的发病率和进展，但其对其他恶性肿瘤（如乳腺癌和子宫内膜癌）的影响仍存在争议，GLP-1RAs可能表现出情境依赖性的促肿瘤效应。然而，基于当前证据，肠促胰岛素激素和GCG在癌症治疗中的获益似乎大于风险。本综述认为，靶向肠促胰岛素和GCG信号通路在肿瘤学中具有相当大的前景，但需要更深入的机制理解和更仔细的患者分层，以充分发挥其临床效用，同时将潜在风险降至最低。
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and therapies targeting glucose-dependent insulinotropic polypeptide (GIP) have demonstrated efficacy in the treatment of type 2 diabetes (T2D) and obesity. GLP-1 and GIP are collectively referred to as incretins. The strong epidemiological link between T2D/obesity and cancer risk suggests that GLP-1 and GIP may serve a substantial role in tumor metabolism. The effects of incretin hormones and the counter-regulatory hormone glucagon (GCG) on tumor biology may have important implications for understanding tumor microenvironmental regulation and for informing cancer therapy. The present review summarizes the mechanisms by which these hormones influence the tumor microenvironment. Beyond the fundamental biology of incretins and GCG, the present review details how GLP-1RAs regulate immune cell functions, including the functions of T cells, neutrophils, natural killer cells and macrophages, to foster an antitumor immune microenvironment. Furthermore, the present review explores their roles in tumor metabolic reprogramming, affecting tumor cell cycle progression, extracellular matrix remodeling and mitochondrial function. Although preclinical and clinical data suggest that GLP-1RAs can reduce the incidence and progression of certain obesity-related cancer types, such as pancreatic and liver cancer, their impact on other malignancies, such as breast and endometrial cancer, remains controversial, with GLP-1RAs potentially exhibiting context-dependent pro-tumor effects. However, based on current evidence, the benefits of incretin hormones and GCG in cancer therapy appear to outweigh the risks. The present review suggests that targeting incretin and GCG signaling holds considerable promise in oncology, but necessitates a deeper mechanistic understanding and more careful patient stratification to fully harness its clinical utility while minimizing potential risks.
如何引用
AMA
Min Hu, Chang-Jun Jiang, Cheng Yi. Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).. Experimental and therapeutic medicine. 2026; doi:10.3892/etm.2026.13178.
APA
Min Hu, Chang-Jun Jiang, Cheng Yi (2026). Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).. Experimental and therapeutic medicine. https://doi.org/10.3892/etm.2026.13178
GB/T 7714
Min Hu, Chang-Jun Jiang, Cheng Yi. Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).[J]. Experimental and therapeutic medicine, 2026 doi:10.3892/etm.2026.13178.
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