Modifying metabolic and immune hallmarks of cancer by a copper complex  

作　　者：Chengyan Chu Yunhua Zhang Chengyuan Qian Xiu-Zhi Yang Yicun Shang Zijian Guo Xiaoyong Wang 

机构地区：[1]State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University,Nanjing 210023,China [2]State Key Laboratory of Coordination Chemistry,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023,China

出　　处：《Science China Chemistry》2025年第3期1051-1066,共16页中国科学(化学英文版)

基　　金：the National Natural Science Foundation of China (22377053,92153303,22293051);the Natural Science Foundation of Jiangsu Province (BK20202004)。

摘　　要：Metabolic adaptation of cancer cells is a key tactic for maintaining their tumorigenicity and viability in the tumor immune microenvironment(TIME).Concurrent modulation on the metabolic pathway and immune system could change the living condition of cancer cells and potentiate the efficacy of anticancer drugs.A copper complex(DDCu)was designed to influence the energy metabolism of cancer cells and reshape the TIME.DDCu restrained the production and transportation of lactate by inhibiting the expression of lactate dehydrogenase and monocarboxylate transporter 4,thereby altering the metabolic pathway of cancer cells and improving the acidic tumor microenvironment.Meantime,DDCu was reduced to Cu~+by cellular glutathione to react with lipoylated proteins of the tricarboxylic acid cycle and destabilize the Fe-S cluster proteins,leading to the aggregation of dihydrolipoamide S-acetyltransferase and cuproptosis in cancer cells.Furthermore,DDCu promoted the polarization of macrophages from the M2 to M1 phenotype,activated CD4^(+)and CD8^(+)T cells,and reversed the immunosuppression.As a result,DDCu inhibited the tumor growth through a synergy between metabolic regulation and immunomodulation.

关 键 词：cancer hallmark copper complex cuproptosis lactate metabolism IMMUNOMODULATION 

分 类 号：R730[医药卫生—肿瘤] O641.4[医药卫生—临床医学]