
浏览全部资源
扫码关注微信
武汉大学人民医院肿瘤中心,武汉 430060
王之顼,Email:zhixu_wang@whu.edu.cn,研究方向:恶性肿瘤的免疫治疗。
章必成,Email:bichengzhang@hotmail.com。
收稿:2024-11-10,
修回:2024-12-06,
录用:2025-02-08,
纸质出版:2025-06-28
移动端阅览
王之顼,宋羽霄,章必成.肿瘤微环境内巨噬细胞和T细胞的多胺代谢重编程[J].重庆医科大学学报,2025,50(6):721-725.
Wang Zhixu,Song Yuxiao,Zhang Bicheng.Metabolic reprogramming of polyamines in macrophages and T cells within the tumor microenvironment[J].Journal of Chongqing Medical University,2025,50(6):721-725.
王之顼,宋羽霄,章必成.肿瘤微环境内巨噬细胞和T细胞的多胺代谢重编程[J].重庆医科大学学报,2025,50(6):721-725. DOI: 10.13406/j.cnki.cyxb.003802.
Wang Zhixu,Song Yuxiao,Zhang Bicheng.Metabolic reprogramming of polyamines in macrophages and T cells within the tumor microenvironment[J].Journal of Chongqing Medical University,2025,50(6):721-725. DOI: 10.13406/j.cnki.cyxb.003802.
在肿瘤微环境(tumor microenvironment,TME)中,巨噬细胞与T细胞的代谢重编程在免疫抑制状态形成及肿瘤免疫逃逸中起关键作用。多胺作为关键信号分子及生物合成前体,其代谢状态深刻调控肿瘤细胞与免疫细胞功能。TME内的细胞因子及其他物质通过诱导多胺代谢相关酶表达,驱动多胺代谢重编程,影响巨噬细胞极化与T细胞分化;同时,多胺代谢重编程导致TME内多胺资源被竞争性消耗,促使肿瘤细胞优化代谢策略以获取生存优势,并抑制免疫细胞功能。因此,多胺代谢抑制剂通过调控代谢重编程,具有成为抗肿瘤治疗药物的潜力。
In the tumor microenvironment(TME),the metabolic reprogramming of macrophages and T cells plays a critical role in the formation of an immunosuppressive state and tumor immune escape. Polyamines are key signaling molecules and precursors for biosynthesis,and the metabolic state of polyamines profoundly regulate the functions of tumor cells and immune cells. Cytokines and other substances within the TME induce the expression of enzymes related to polyamine metabolism,drive the metabolic reprogramming of polyamines,and thus influence macrophage polarization and T cell differentiation; meanwhile,the metabolic reprogramming of polyamines leads to the competitive depletion of polyamine resources within the TME,promote tumor cells to optimize their metabolic strategies for survival advantages,and inhibit the function of immune cells. Therefore,inhibitors of polyamine metabolism may be used as antitumor drugs by regulating metabolic reprogramming.
Sahu PN , Sen A . Preventing cancer by inhibiting ornithine decarboxylase:a comparative perspective on synthetic vs. natural drugs [J ] . Chem Biodivers , 2024 , 21 ( 4 ): e202302067
Tse RT , Wong CY , Chiu PK , et al . The potential role of spermine and its acetylated derivative in human malignancies [J ] . Int J Mol Sci , 2022 , 23 ( 3 ): 1258 .
Wang N , Chai MY , Zhu LY , et al . Development and validation of polyamines metabolism-associated gene signatures to predict prognosis and immunotherapy response in lung adenocarcinoma [J ] . Front Immunol , 2023 , 14 : 1070953 .
Chamoto K , Zhang BH , Tajima M , et al . Spermidine - an old molecule with a new age-defying immune function [J ] . Trends Cell Biol , 2024 , 34 ( 5 ): 363 - 370 .
Uemura T , Matsunaga M , Yokota Y , et al . Inhibition of polyamine catabolism reduces cellular senescence [J ] . Int J Mol Sci , 2023 , 24 ( 17 ): 13397 .
Fujii J , Imai H . Oxidative metabolism as a cause of lipid peroxidation in the execution of ferroptosis [J ] . Int J Mol Sci , 2024 , 25 ( 14 ): 7544 .
Ivanova ON , Gavlina AV , Karpenko IL , et al . Polyamine catabolism revisited:acetylpolyamine oxidase plays a minor role due to low expression [J ] . Cells , 2024 , 13 ( 13 ): 1134 .
Latour YL , Gobert AP , Wilson KT . The role of polyamines in the regulation of macrophage polarization and function [J ] . Amino Acids , 2020 , 52 ( 2 ): 151 - 160 .
Liu QQ , Yan XY , Li RY , et al . Polyamine signal through HCC microenvironment:a key regulator of mitochondrial preservation and turnover in TAMs [J ] . Int J Mol Sci , 2024 , 25 ( 2 ): 996 .
Hu XY , Li J , Fu MR , et al . The JAK/STAT signaling pathway:from bench to clinic [J ] . Signal Transduct Target Ther , 2021 , 6 ( 1 ): 402 .
Coni S , Bordone R , Ivy DM , et al . Combined inhibition of polyamine metabolism and eIF5A hypusination suppresses colorectal cancer growth through a converging effect on MYC translation [J ] . Cancer Lett , 2023 , 559 : 216120 .
Song WT , Tiruthani K , Wang Y , et al . Trapping of lipopolysaccharide to promote immunotherapy against colorectal cancer and attenuate liver metastasis [J ] . Adv Mater , 2018 , 30 ( 52 ): e1805007 .
Su PF , Li O , Ke K , et al . Targeting tumor-associated macrophages:critical players in tumor progression and therapeutic strategies (review) [J ] . Int J Oncol , 2024 , 64 ( 6 ): 60 .
Puleston DJ , Buck MD , Klein Geltink RI , et al . Polyamines and eIF5A hypusination modulate mitochondrial respiration and macrophage activation [J ] . Cell Metab , 2019 , 30 ( 2 ): 352 - 363 .
Lapi I , Daskalaki MG , Axarlis K , et al . AKT isoforms in macrophage activation,polarization,and survival [J ] . Curr Top Microbiol Immunol , 2022 , 436 : 165 - 196 .
Wu RH , Chen XY , Kang SW , et al . De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function [J ] . Sci Adv , 2020 , 6 ( 51 ): eabc4275 .
Stewart TM , Holbert CE , Jr Casero RA . Helping the helpers:polyamines help maintain helper T-cell lineage fidelity [J ] . Immunometabolism , 2022 , 4 ( 3 ): e00002 .
Elmarsafawi AG , Hesterberg RS , Fernandez MR , et al . Modulating the polyamine/hypusine axis controls generation of CD8 + tissue-resident memory T cells [J ] . JCI Insight , 2023 , 8 ( 18 ): e169308 .
Zeng JC , Ye ZY , Shi SH , et al . Targeted inhibition of eIF5A hpu suppresses tumor growth and polarization of M2-like tumor-associated macrophages in oral cancer [J ] . Cell Death Dis , 2023 , 14 ( 8 ): 579 .
Wagner A , Wang C , Fessler J , et al . Metabolic modeling of single Th17 cells reveals regulators of autoimmunity [J ] . Cell , 2021 , 184 ( 16 ): 4168 - 4185 .
Zhang HX , Li SZ , Wang D , et al . Metabolic reprogramming and immune evasion:the interplay in the tumor microenvironment [J ] . Biomark Res , 2024 , 12 ( 1 ): 96 .
Carriche GM , Almeida L , Stüve P , et al . Regulating T-cell differentiation through the polyamine spermidine [J ] . J Allergy Clin Immunol , 2021 , 147 ( 1 ): 335 - 348 .
Guo ZY , Zhang X , Lin CJ , et al . METTL3-IGF 2 BP 3 -axis mediates the proliferation and migration of pancreatic cancer by regulating spermine synthase m6A modification [J ] . Front Oncol , 2022 , 12 : 962204 .
Holbert CE , Cullen MT , Jr Casero RA , et al . Polyamines in cancer:integrating organismal metabolism and antitumour immunity [J ] . Nat Rev Cancer , 2022 , 22 ( 8 ): 467 - 480 .
Van den Bossche J . Colonic macrophages eat and feed [J ] . Cell Metab , 2023 , 35 ( 11 ): 1847 - 1848 .
Li X , Wang SM , Mu W , et al . Reactive oxygen species reprogram macrophages to suppress antitumor immune response through the exosomal miR-155-5p/PD-L1 pathway [J ] . J Exp Clin Cancer Res , 2022 , 41 ( 1 ): 41 .
Grobben Y . Targeting amino acid-metabolizing enzymes for cancer immunotherapy [J ] . Front Immunol , 2024 , 15 : 1440269 .
Miska J , Rashidi A , Lee-Chang C , et al . Polyamines drive myeloid cell survival by buffering intracellular pH to promote immunosuppression in glioblastoma [J ] . Sci Adv , 2021 , 7 ( 8 ): eabc8929 .
Zeng JC , Zhang YC , Fang YM , et al . Natural product quercetin-3-methyl ether promotes colorectal cancer cell apoptosis by downregulating intracellular polyamine signaling [J ] . Int J Med Sci , 2024 , 21 ( 5 ): 904 - 913 .
Sun LD , Yang JL , Qin Y , et al . Discovery and antitumor evaluation of novel inhibitors of spermine oxidase [J ] . J Enzyme Inhib Med Chem , 2019 , 34 ( 1 ): 1140 - 1151 .
Furbish AB , Alford AS , Burger P , et al . Identification and characterization of novel small-molecule SMOX inhibitors [J ] . Med Sci , 2022 , 10 ( 3 ): 47 .
Di Paolo ML , Cervelli M , Mariottini P , et al . Exploring the activity of polyamine analogues on polyamine and spermine oxidase:methoctramine,a potent and selective inhibitor of polyamine oxidase [J ] . J Enzyme Inhib Med Chem , 2019 , 34 ( 1 ): 740 - 752 .
Alexander ET , Mariner K , Donnelly J , et al . Polyamine blocking therapy decreases survival of tumor-infiltrating immunosuppressive myeloid cells and enhances the antitumor efficacy of PD-1 blockade [J ] . Mol Cancer Ther , 2020 , 19 ( 10 ): 2012 - 2022 .
0
浏览量
12
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621