Xiang Hong, Yang Runjuan, Tu Jiaxin, Xi Yan, Yang Shilei, Lv Linlin, Zhai Xiaohan, Zhu Yanna, Dong Deshi, Tao Xufeng
Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, 116011 Dalian, China.
Department of Pharmacy, First Affiliated Hospital of Dalian Medical University, 116011 Dalian, China; School of pharmacy, Dalian Medical University, 116044 Dalian, China.
Biomed Pharmacother. 2023 Jan;157:113992. doi: 10.1016/j.biopha.2022.113992. Epub 2022 Nov 14.
Abnormal intracellular metabolism not only provides nutrition for tumor occurrence and development, but also sensitizes the function of various immune cells in the immune microenvironment to promote tumor immune escape. This review discusses the emerging role of immune cells in the progress of pancreatic cancer, acrossing metabolic reprogramming and key metabolic pathways present in different immune cell types. At present, the hotspots of metabolic reprogramming of immune cells in pancreatic cancer progression mainly focuses on glucose metabolism, lipid metabolism, tricarboxylic acid cycle and amino acid metabolism, which affect the function of anti-tumor immune cells and immunosuppressive cells in the microenvironment, such as macrophages, dendritic cells, T cells, myeloid-derived suppressor cells, neutrophils and B cells by a series of key metabolic signaling pathways, such as PI3K/AKT, mTOR, AMPK, HIF-1α, c-Myc and p53. Drugs that target the tumor metabolism pathways for clinical treatment of pancreatic cancer are also systematically elaborated, which may constitute food for others' projects involved in clinical anti-cancer research.
异常的细胞内代谢不仅为肿瘤的发生和发展提供营养,还使免疫微环境中各种免疫细胞的功能敏感化,从而促进肿瘤免疫逃逸。本文综述了免疫细胞在胰腺癌进展中的新作用,涉及代谢重编程以及不同免疫细胞类型中存在的关键代谢途径。目前,胰腺癌进展中免疫细胞代谢重编程的热点主要集中在糖代谢、脂代谢、三羧酸循环和氨基酸代谢,这些代谢通过一系列关键代谢信号通路,如PI3K/AKT、mTOR、AMPK、HIF-1α、c-Myc和p53,影响微环境中抗肿瘤免疫细胞和免疫抑制细胞的功能,如巨噬细胞、树突状细胞、T细胞、髓源性抑制细胞、中性粒细胞和B细胞。还系统阐述了针对肿瘤代谢途径用于胰腺癌临床治疗的药物,这可能为其他参与临床抗癌研究的项目提供思路。