Shijuan Jiang , Bo Ren , Chen Ding , Changwei Du, Zhe Cao, Gang Yang, Hua Huang, Taiping Zhang
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引用次数: 0
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, characterized by its aggressiveness and poor outcomes. Emerging evidence implicates dysregulated polyamine metabolism as a key driver of PDAC immunosuppression, yet the mechanisms underlying this metabolic-immune crosstalk remain poorly defined. This review summarizes recent findings demonstrating that PDAC is uniquely dependent on glutamine-derived ornithine for de novo polyamine synthesis, orchestrated by the KRAS-MYC axis. Through metabolic reprogramming of immune cells, polyamines polarize tumor-associated macrophages toward M2-like phenotypes, expand myeloid-derived suppressor cells, and impair T cell activation. Crucially, the immunomodulatory effects of polyamines are source-dependent: tumor-derived spermidine promotes T cell exhaustion, whereas dietary spermidine enhances antitumor immunity through fatty acid oxidation. Preclinical studies have highlighted that polyamine-targeted therapy, including biosynthesis inhibitors, arginine deprivation agents and polyamine analogue, is a promising strategy to reverse immunosuppression and enhance the efficacy of checkpoint inhibitors. These evidences establish polyamine metabolism as a therapeutic vulnerability in PDAC, offering novel diagnostic tools and combination regimens to overcome therapeutic resistance.
期刊介绍:
Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research.
Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy.
By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.