Effect of amino acid metabolic reprogramming on immune microenvironment of hepatocellular carcinoma

Xiaoli LIU; Qinwen TAN; Jian XU; Huanling CHEN; Jie YU; Lu LU; Mingkan DAI; Jingjing HUANG; Hongna HUANG; Dewen MAO

doi:10.12449/JCH241226

Volume 40 Issue 12

Dec. 2024

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2024 > 40(12): 2531-2537

PDF( 1054 KB)

Effect of amino acid metabolic reprogramming on immune microenvironment of hepatocellular carcinoma

DOI: 10.12449/JCH241226

1.
Graduate School of Guangxi University of Chinese Medicine，Nanning 530200，China
2a.
Department of Spleen，Stomach and Hepatology，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China
2b.
Department of Traditional Chinese Internal Medicine，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China
2c.
Department of Hepatology，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China

Research funding:

National Natural Science Foundation of China (82460957);

Guangxi Natural Science Foundation (2024GXNSFDA010005);

Guangxi Natural Science Foundation (2022GXNSFAA035460);

Guangxi Natural Science Foundation (2022GXNSFBA035485);

Project of Introducing Doctoral Scientific Research Start-up Fund of Guangxi University of Traditional Chinese Medicine (2022BS026);

Guangxi Postgraduate Education Innovation Programme (YCSW2023395)

More Information

Corresponding author: HUANG Jingjing， 55869563@qq.com （ORCID： 0000-0002-4936-0838）
Received Date: 2024-04-13
Accepted Date: 2024-07-04
Published Date: 2024-12-25

Abstract

Abstract

Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells， and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma， amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention， showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy， its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice， in order to provide new ideas for immunotherapy for liver cancer.
- Carcinoma， Hepatocellular,
- Tumor Microenvironment,
- Amino Acids,
- Metabolism,
- Immunomodulation

FullText(HTML)

References(43)

References

[1]	ZHENG YL, LI L, JIA YX, et al. LINC01554-mediated glucose metabolism reprogramming suppresses tumorigenicity in hepatocellular carcinoma via downregulating PKM2 expression and inhibiting Akt/mTOR signaling pathway[J]. Theranostics, 2019, 9( 3): 796- 810. DOI: 10.7150/thno.28992.
[2]	RUMGAY H, ARNOLD M, FERLAY J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040[J]. J Hepatol, 2022, 77( 6): 1598- 1606. DOI: 10.1016/j.jhep.2022.08.021.
[3]	Department of Medical Emergency, National Health Commission of the People’s Republic of China. Healthy China action-implementation plan of cancer prevention action(2023-2030)[J]. China Cancer, 2023, 32( 12): 887- 890. DOI: 10.11735/j.issn.1004-0242.2023.12.A001. 中华人民共和国国家卫生健康委员会医疗应急司. 健康中国行动——癌症防治行动实施方案(2023—2030年)[J]. 中国肿瘤, 2023, 32( 12): 887- 890. DOI: 10.11735/j.issn.1004-0242.2023.12.A001.
[4]	NONG SQ, HAN XY, XIANG Y, et al. Metabolic reprogramming in cancer: Mechanisms and therapeutics[J]. MedComm(2020), 2023, 4( 2): e218. DOI: 10.1002/mco2.218.
[5]	FOGLIA B, BELTRÀ M, SUTTI S, et al. Metabolic reprogramming of HCC: A new microenvironment for immune responses[J]. Int J Mol Sci, 2023, 24( 8): 7463. DOI: 10.3390/ijms24087463.
[6]	PAGET S. The distribution of secondary growths in cancer of the breast. 1889[J]. Cancer Metastasis Rev, 1989, 8( 2): 98- 101.
[7]	ZHANG Q, LOU Y, BAI XL, et al. Immunometabolism: A novel perspective of liver cancer microenvironment and its influence on tumor progression[J]. World J Gastroenterol, 2018, 24( 31): 3500- 3512. DOI: 10.3748/wjg.v24.i31.3500.
[8]	KOTSARI M, DIMOPOULOU V, KOSKINAS J, et al. Immune system and hepatocellular carcinoma(HCC): New insights into HCC progression[J]. Int J Mol Sci, 2023, 24( 14): 11471. DOI: 10.3390/ijms241411471.
[9]	PAULUSMA CC, LAMERS WH, BROER S, et al. Amino acid metabolism, transport and signalling in the liver revisited[J]. Biochem Pharmacol, 2022, 201: 115074. DOI: 10.1016/j.bcp.2022.115074.
[10]	ZHENG Y, YAO YR, GE TX, et al. Amino acid metabolism reprogramming: Shedding new light on T cell anti-tumor immunity[J]. J Exp Clin Cancer Res, 2023, 42( 1): 291. DOI: 10.1186/s13046-023-02845-4.
[11]	ZHANG XH, ZHANG SY, LI L. Amino acid metabolic reprogramming in tumorigenesis and development[J]. Chin J Biochem Mol Biol, 2023, 39( 2): 174- 188. DOI: 10.13865/j.cnki.cjbmb.2022.06.1105. 张仙宏, 张思雨, 李乐. 氨基酸代谢重编程在肿瘤发生发展中的作用[J]. 中国生物化学与分子生物学报, 2023, 39( 2): 174- 188. DOI: 10.13865/j.cnki.cjbmb.2022.06.1105.
[12]	YANG F, HILAKIVI-CLARKE L, SHAHA A, et al. Metabolic reprogramming and its clinical implication for liver cancer[J]. Hepatology, 2023, 78( 5): 1602- 1624. DOI: 10.1097/HEP.0000000000000005.
[13]	WANG YY, BAI CS, RUAN YX, et al. Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia[J]. Nat Commun, 2019, 10( 1): 201. DOI: 10.1038/s41467-018-08033-9.
[14]	JIN HJ, WANG SY, ZAAL EA, et al. A powerful drug combination strategy targeting glutamine addiction for the treatment of human liver cancer[J]. eLife, 2020, 9: e56749. DOI: 10.7554/eLife.56749.
[15]	LIN J, RAO DN, ZHANG M, et al. Metabolic reprogramming in the tumor microenvironment of liver cancer[J]. J Hematol Oncol, 2024, 17( 1): 6. DOI: 10.1186/s13045-024-01527-8.
[16]	TIAN LY, SMIT DJ, JÜCKER M. The role of PI3K/AKT/mTOR signaling in hepatocellular carcinoma metabolism[J]. Int J Mol Sci, 2023, 24( 3): 2652. DOI: 10.3390/ijms24032652.
[17]	MERLIN J, IVANOV S, DUMONT A, et al. Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation[J]. Nat Metab, 2021, 3( 10): 1313- 1326. DOI: 10.1038/s42255-021-00471-y.
[18]	MA GF, ZHANG ZL, LI P, et al. Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment[J]. Cell Commun Signal, 2022, 20( 1): 114. DOI: 10.1186/s12964-022-00909-0.
[19]	YE YY, YU BD, WANG H, et al. Glutamine metabolic reprogramming in hepatocellular carcinoma[J]. Front Mol Biosci, 2023, 10: 1242059. DOI: 10.3389/fmolb.2023.1242059.
[20]	PENG H, WANG YF, LUO WB. Multifaceted role of branched-chain amino acid metabolism in cancer[J]. Oncogene, 2020, 39( 44): 6747- 6756. DOI: 10.1038/s41388-020-01480-z.
[21]	BONVINI A, ROGERO MM, COQUEIRO AY, et al. Effects of different branched-chain amino acids supplementation protocols on the inflammatory response of LPS-stimulated RAW 264.7 macrophages[J]. Amino Acids, 2021, 53( 4): 597- 607. DOI: 10.1007/s00726-021-02940-w.
[22]	LING ZN, JIANG YF, RU JN, et al. Amino acid metabolism in health and disease[J]. Signal Transduct Target Ther, 2023, 8( 1): 345. DOI: 10.1038/s41392-023-01569-3.
[23]	HU GY, CUI Z, CHEN XY, et al. Suppressing mesenchymal stromal cell ferroptosis via targeting a metabolism-epigenetics axis corrects their poor retention and insufficient healing benefits in the injured liver milieu[J]. Adv Sci(Weinh), 2023, 10( 13): e2206439. DOI: 10.1002/advs.202206439.
[24]	MOSSMANN D, MÜLLER C, PARK S, et al. Arginine reprograms metabolism in liver cancer via RBM39[J]. Cell, 2023, 186( 23): 5068- 5083. DOI: 10.1016/j.cell.2023.09.011.
[25]	LÍNDEZ AA MI, REITH W. Arginine-dependent immune responses[J]. Cell Mol Life Sci, 2021, 78( 13): 5303- 5324. DOI: 10.1007/s00018-021-03828-4.
[26]	SICA A, PORTA C, MORLACCHI S, et al. Origin and functions of tumor-associated myeloid cells(TAMCs)[J]. Cancer Microenviron, 2012, 5( 2): 133- 149. DOI: 10.1007/s12307-011-0091-6.
[27]	YANG LM, CHU ZL, LIU M, et al. Amino acid metabolism in immune cells: Essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy[J]. J Hematol Oncol, 2023, 16( 1): 59. DOI: 10.1186/s13045-023-01453-1.
[28]	MISSIAEN R, ANDERSON NM, KIM LC, et al. GCN2 inhibition sensitizes arginine-deprived hepatocellular carcinoma cells to senolytic treatment[J]. Cell Metab, 2022, 34( 8): 1151- 1167. DOI: 10.1016/j.cmet.2022.06.010.
[29]	TRÉZÉGUET V, FATROUNI H, MERCHED AJ. Immuno-metabolic modulation of liver oncogenesis by the tryptophan metabolism[J]. Cells, 2021, 10( 12): 3469. DOI: 10.3390/cells10123469.
[30]	SOLVAY M, HOLFELDER P, KLAESSENS S, et al. Tryptophan depletion sensitizes the AHR pathway by increasing AHR expression and GCN2/LAT1-mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes[J]. J Immunother Cancer, 2023, 11( 6): e006728. DOI: 10.1136/jitc-2023-006728.
[31]	CAMPESATO LF, BUDHU S, TCHAICHA J, et al. Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine[J]. Nat Commun, 2020, 11( 1): 4011. DOI: 10.1038/s41467-020-17750-z.
[32]	DEY S, MONDAL A, DUHADAWAY JB, et al. IDO1 signaling through GCN2 in a subpopulation of gr-1⁺ cells shifts the IFNγ/IL6 balance to promote neovascularization[J]. Cancer Immunol Res, 2021, 9( 5): 514- 528. DOI: 10.1158/2326-6066.CIR-20-0226.
[33]	HEZAVEH K, SHINDE RS, KLÖTGEN A, et al. Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity[J]. Immunity, 2022, 55( 2): 324- 340. DOI: 10.1016/j.immuni.2022.01.006.
[34]	GIRITHAR HN, STAATS PIRES A, AHN SB, et al. Involvement of the kynurenine pathway in breast cancer: Updates on clinical research and trials[J]. Br J Cancer, 2023, 129( 2): 185- 203. DOI: 10.1038/s41416-023-02245-7.
[35]	LONG G, WANG D, TANG JN, et al. Development of tryptophan metabolism patterns to predict prognosis and immunotherapeutic responses in hepatocellular carcinoma[J]. Aging(Albany NY), 2023, 15( 15): 7593- 7615. DOI: 10.18632/aging.204928.
[36]	PASCALE RM, PEITTA G, SIMILE MM, et al. Alterations of methionine metabolism as potential targets for the prevention and therapy of hepatocellular carcinoma[J]. Medicina(Kaunas), 2019, 55( 6): 296. DOI: 10.3390/medicina55060296.
[37]	ROY DG, CHEN J, MAMANE V, et al. Methionine metabolism shapes T helper cell responses through regulation of epigenetic reprogramming[J]. Cell Metab, 2020, 31( 2): 250- 266. DOI: 10.1016/j.cmet.2020.01.006.
[38]	HUNG MH, LEE JS, MA C, et al. Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma[J]. Nat Commun, 2021, 12( 1): 1455. DOI: 10.1038/s41467-021-21804-1.
[39]	SINCLAIR LV, HOWDEN AJ, BRENES A, et al. Antigen receptor control of methionine metabolism in T cells[J]. eLife, 2019, 8: e44210. DOI: 10.7554/eLife.44210.
[40]	SAINI N, NAAZ A, METUR SP, et al. Methionine uptake via the SLC43A2 transporter is essential for regulatory T-cell survival[J]. Life Sci Alliance, 2022, 5( 12): e202201663. DOI: 10.26508/lsa.202201663.
[41]	LI JT, YANG H, LEI MZ, et al. Dietary folate drives methionine metabolism to promote cancer development by stabilizing MAT IIA[J]. Signal Transduct Target Ther, 2022, 7( 1): 192. DOI: 10.1038/s41392-022-01017-8.
[42]	VOGEL A, MEYER T, SAPISOCHIN G, et al. Hepatocellular carcinoma[J]. Lancet, 2022, 400: 1345- 1362. DOI: 10.1016/S0140-6736(22)01200-4.
[43]	ENDICOTT M, JONES M, HULL J. Amino acid metabolism as a therapeutic target in cancer: A review[J]. Amino Acids, 2021, 53( 8): 1169- 1179. DOI: 10.1007/s00726-021-03052-1.

Relative Articles

[1]	Qiulu ZHANG, Zhuo LI, Congrong LIU, Limei GUO. Components of tumor stroma-immune microenvironment and their interactions in intrahepatic cholangiocarcinoma[J]. Journal of Clinical Hepatology, 2025, 41(3): 594-600. doi: 10.12449/JCH250331
[2]	Peipei GUO, Yang XU, Jiaqi SHI, Yang WU, Lixia LU, Bin LI, Xiaohui YU. Role of amino acid metabolism in autoimmune hepatitis and related therapeutic targets[J]. Journal of Clinical Hepatology, 2025, 41(3): 547-551. doi: 10.12449/JCH250323
[3]	Hui ZHANG, Ming TAN, Shengtao CHENG, Juan CHEN. Mechanism of amino acid metabolism in nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2024, 40(4): 810-815. doi: 10.12449/JCH240427
[4]	Xiaohua ZHANG, Ying FENG, Xianbo WANG. Role of the Hedgehog signaling pathway in hepatocellular carcinoma and its tumor microenvironment[J]. Journal of Clinical Hepatology, 2024, 40(4): 822-827. doi: 10.12449/JCH240429
[5]	Jun LIU, Ling WANG, Yuhuan JIANG, Jingzhi WANG, Huiming LI. Establishment of a risk model based on immunogenic cell death-related genes and its value in predicting the prognosis and tumor microenvironment characteristics of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2024, 40(12): 2473-2483. doi: 10.12449/JCH241218
[6]	Peng WANG, Jiannan QIU, Zhongxia WANG, Junhua WU, Chunping JIANG. Research advances in tumor-associated macrophages in hepatocellular carcinoma microenvironment[J]. Journal of Clinical Hepatology, 2023, 39(5): 1212-1218. doi: 10.3969/j.issn.1001-5256.2023.05.033
[7]	Yanxin TIAN, Na LI, Lei GAO, Jia WU, Ying ZHU. Influence of the interaction between tumor microenvironment and liver cancer stem cells on the development and progression of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2023, 39(3): 684-692. doi: 10.3969/j.issn.1001-5256.2023.03.032
[8]	Faxiang MA, Zhengkun TU. Role of purine signaling in liver immune regulation[J]. Journal of Clinical Hepatology, 2023, 39(6): 1488-1496. doi: 10.3969/j.issn.1001-5256.2023.06.036
[9]	Chaoran YANG, Sirou LI, Yuan LIU, Zhiyuan HOU, Yuan WANG, Jihong YANG. Role of non-coding RNA on immune cells in tumor microenvironment of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2023, 39(4): 961-967. doi: 10.3969/j.issn.1001-5256.2023.04.033
[10]	Fan YAO, Xin YIN. Regulatory effect of immune checkpoint TIGIT/CD155 on the immune microenvironment of primary liver cancer and its application prospects[J]. Journal of Clinical Hepatology, 2022, 38(11): 2632-2635. doi: 10.3969/j.issn.1001-5256.2022.11.039
[11]	Mingqiang ZHU, Youming DING. Current status of the research on microenvironment-targeting therapy and immunotherapy for liver cancer[J]. Journal of Clinical Hepatology, 2022, 38(8): 1913-1917. doi: 10.3969/j.issn.1001-5256.2022.08.038
[12]	Yiyi ZHANG, Min XU. Research advances in the mechanism of tumor microenvironment in pancreatic cancer and related targeted therapy[J]. Journal of Clinical Hepatology, 2022, 38(4): 965-968. doi: 10.3969/j.issn.1001-5256.2022.04.046
[13]	Yi CHEN, Li XIE, Jian WU. Role of KRAS mutation in metabolism of pancreatic ductal adenocarcinoma[J]. Journal of Clinical Hepatology, 2022, 38(12): 2901-2907. doi: 10.3969/j.issn.1001-5256.2022.12.043
[14]	Shun CHEN, Jun WANG. Advances in tumor microenvironment and immunotherapy of Cholangiocarcinoma[J]. Journal of Clinical Hepatology, 2022, 38(10): 2428-2432. doi: 10.3969/j.issn.1001-5256.2022.10.044
[15]	Xueyan LI, Changjun WANG. Influence of hepatocellular carcinoma microenvironment on myeloid-derived suppressor cells[J]. Journal of Clinical Hepatology, 2021, 37(6): 1473-1476. doi: 10.3969/j.issn.1001-5256.2021.06.053
[16]	Feiyu ZHANG, Yakepu ADILA, Jinming ZHAO, Yanhang GAO. New advances in the treatment of pancreatic cancer by targeting tumor microenvironment[J]. Journal of Clinical Hepatology, 2021, 37(9): 2246-2248. doi: 10.3969/j.issn.1001-5256.2021.09.049
[17]	Wang ShanShan, Zhang QingShan, Zhao SuXian, Kong LingBo, Ji Lei, Kong Li. The immunoregulatory effect of tumor necrosis factor-alpha-induced protein 8-like 2 in different liver diseases[J]. Journal of Clinical Hepatology, 2020, 36(2): 460-463. doi: 10.3969/j.issn.1001-5256.2020.02.050
[18]	Wu Jing, Meng QingHua, Xue Ran. Effect of tumor-stroma crosstalk on amino acid metabolism in hepatic stellate cells[J]. Journal of Clinical Hepatology, 2018, 34(12): 2610-2613. doi: 10.3969/j.issn.1001-5256.2018.12.020
[19]	Zhao YuPing, Han XiuQing, Xue ShuBao, Xiao FengYan, Gao CuiHong, Zhao LiMei. Clinical analysis of blood amino acids and trace elements in patients with hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2015, 31(6): 915-917. doi: 10.3969/j.issn.1001-5256.2015.06.021
[20]	Zhang ZhanQing, Lu Wei, Wang YanBing, Jia XiaoFang, Zhang LiJun, Ding RongRong, Zhou XinLan, Feng YanLing. Diagnosis of hepatic fibrosis in hepatitis B patients by logistic regression modeling based on plasma amino acid ratio and age[J]. Journal of Clinical Hepatology, 2013, 29(5): 330-335.

Supplements(0)

Cited By

Cited by
Periodical cited type(1)
1. 邵旭，徐岷，戴宇飞，张逸然. 糖酵解在结直肠癌中的研究进展. 现代消化及介入诊疗. 2024(12): 1469-1472 .
Other cited types(0)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(1)

Get Citation

PDF

XML

Article Metrics

Article views (319) PDF downloads(25)

Effect of amino acid metabolic reprogramming on immune microenvironment of hepatocellular carcinoma

DOI: 10.12449/JCH241226

Abstract

References

Relative Articles

Cited by

Periodical cited type(1)

Other cited types(0)

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Effect of amino acid metabolic reprogramming on immune microenvironment of hepatocellular carcinoma

DOI: 10.12449/JCH241226

Abstract

References

Relative Articles

Cited by

Periodical cited type(1)

Other cited types(0)

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content