厦门大学林圣彩团队取得一项新突破。他们揭示了葡萄糖饥饿模拟aldometanib消除免疫屏障，使肝细胞癌小鼠活到正常年龄。相关论文于2025年11月25日发表在《细胞研究》杂志上。

在这项研究中，该课题组人员探索了aldometanib的抗癌治疗作用，它特异性地靶向溶酶体相关醛缩酶来模拟葡萄糖饥饿，从而激活溶酶体AMP激活的蛋白激酶（AMPK），这是代谢稳态的主要调节剂。课题组人员发现aldometanib以AMPK依赖的方式抑制肝细胞癌（HCC）的生长，允许肝癌小鼠存活到成熟年龄，尽管aldometanib对HCC或正常细胞不具有细胞毒性。有趣的是，aldometanib仅在免疫正常的宿主小鼠中发挥抗癌作用，而在免疫缺陷的小鼠中不起作用。该团队还发现，aldometanib治疗小鼠的HCC组织中大量浸润CD8⁺ T细胞，而在肝脏特异性敲除AMPKα的小鼠中未见这种情况。他们的研究结果表明，代谢调节因子AMPK重新平衡肿瘤微环境，使体内的细胞毒性免疫细胞能够消除癌细胞并有效地遏制肿瘤组织。代谢干预可以使癌症成为一种终生可控的疾病，这一发现可能会使他们进入癌症治疗的新时代。

据了解，肿瘤组织和肿瘤旁组织的代谢失调都可能导致免疫抑制，这可能是癌症发展的基础。然而，代谢干预作为一种治疗策略一直无效。

附：英文原文

Title: Glucose starvation mimetic aldometanib removes immune barriers permitting mice with hepatocellular carcinoma to live to normal ages

Author: Hu, Hui-Hui, Wang, Xuefeng, Lan, Bin, Cheng, Haili, Wen, Hong, Chen, Fangfang, Wu, Jianfeng, Li, Mengqi, Chen, Jiazhou, Zhang, Jinhui, Chen, Dongxu, Lin, Shiyu, Lin, Jieyu, Yang, Mingyang, Wu, Zhenhua, Zheng, Zhong-Zheng, Chen, Fuqing, Zhou, Jianyin, Chen, Gang, Chen, Yu, Deng, Xianming, Zhang, Chen-Song, Liu, Jingfeng, Lin, Sheng-Cai

Issue&Volume: 2025-11-25

Abstract: Dysregulated metabolism in tumor tissues and para-tumor tissues alike can lead to immunosuppression, which may underlie cancer development. However, metabolic intervention as a therapeutic strategy has been of no avail. In this study, we explored the anti-cancer therapeutic effect of aldometanib, which specifically targets lysosome-associated aldolase to mimic glucose starvation and thereby activates lysosomal AMP-activated protein kinase (AMPK), a master regulator of metabolic homeostasis. We show that aldometanib inhibits the growth of hepatocellular carcinoma (HCC) in an AMPK-dependent manner, allowing hepatoma-bearing mice to survive to mature ages, although aldometanib does not possess cytotoxicity toward HCC or normal cells. Intriguingly, aldometanib exerts anti-cancer effects only in immune-competent host mice, but not in immune-defective mice. We also found that HCC tissues in aldometanib-treated mice were massively infiltrated with CD8+ T cells, which was not seen in mice with liver-specific knockout of AMPKα. Our findings thus suggest that the metabolic regulator AMPK rebalances the tumor microenvironment to allow cytotoxic immune cells inside the body to eliminate cancer cells and effectively contain the tumor tissues. The finding that metabolic intervention can make cancer a lifelong manageable disease may usher in a new era of cancer therapy.

DOI: 10.1038/s41422-025-01195-4

Source: https://www.nature.com/articles/s41422-025-01195-4