Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors

作者：Jinglei Zhang, Zhuohuan Chu, Jiawen Li, Lu Xie, Cong Ding, Zhe An, Xiang Wang, Hangbin Jin, Xiaofeng Zhang, Qiang Liu, Jianfeng Yang · 发表于：International Journal of Biological Sciences · 年份：2025 · DOI：10.7150/ijbs.122325 · 被引用次数：2 · 研究领域：Cancer, Hypoxia, and Metabolism、Immune cells in cancer、Cancer Research and Treatments

Biliary and pancreatic malignant tumors refer to biliary tract carcinoma (BTC) and pancreatic cancer (PC), among which BTC mainly includes cholangiocarcinoma (CCA) and gallbladder cancer (GBC), and their prognosis is poor because of the lack of effective early diagnostic methods. Although surgical resection is the preferred method for a cure, treatment options are limited for patients with advanced tumors. Therefore, the exploration of other new treatment methods is urgently needed. Currently, metabolic reprogramming is a key mechanism in the process of tumor development and progression and is closely related to cancer cell proliferation, metastasis and drug resistance. As an indispensable part of metabolic reprogramming in tumor cells, amino acid (AA) metabolic reprogramming provides an energy source for tumor cells and participates in regulating the tumor microenvironment (TME). Moreover, as important intrinsic myeloid cells, macrophages play indispensable physiological roles in malignant tumor progression. In the TME, tumor cells can not only induce peripheral immune tolerance by releasing extracellular signals but also compete with tumor-associated macrophages (TAMs) for AAs and release the resulting downstream metabolites into the TME, directly targeting and damaging immune cells and influencing macrophage polarization. Consequently, a more profound understanding of the function of AA metabolic reprogramming in biliopancreatic malignancies and their associated macrophage...