|Table of Contents|

Progress in metabolic reprogramming of tumor-associated macrophages in the hepatocellular carcinoma microenvironment

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 06
Page:
1141-1147
Research Field:
Publishing date:

Info

Title:
Progress in metabolic reprogramming of tumor-associated macrophages in the hepatocellular carcinoma microenvironment
Author(s):
LI Zhaozhao1DU Haichen1LI Weina1WANG Zhaowei1SHI Gege12XIE Fei13SHI Jiaxin13MENG Sainan13MAO Jiyong13WEN Qi13CAO Zhengcong1<
1.Department of Biopharmaceutics,School of Pharmacy,Air Force Medical University,Shaanxi Xi'an 710032,China;2.School of Life Sciences,Northwest University,Shaanxi Xi'an 710069,China;3.School of Basic Medicine,Air Force Medical University,Shaanxi Xi'an 710032,China.
Keywords:
hepatocellular carcinomatumor-associated macrophagesmetabolic reprogrammingimmunotherapy
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2024.06.029
Abstract:
Tumor-associated macrophages (TAMs) are the most abundant immune cells in the liver cancer microenvironment with high plasticity and heterogeneity,which makes them an important subgroup that causes suppressive immune microenvironment of hepatocellular carcinoma (HCC).In order to meet the needs of rapid proliferation,invasion and migration,tumor cells increase their metabolic rate,which results in anoxic and acidic tumor microenvironment (TME).With the occurrence and development of HCC,TAMs constantly reprogram their metabolism to regulate their phenotype and function in order to adapt to the changes in TME.Besides,the metabolites produced in the metabolic reprogramming of TAMs reshape the immune properties of TME and their effects on other immune cells,such as inhibiting the antitumor activity of T lymphocytes and natural killer cells,thus promoting the occurrence,development and metastasis of HCC.This paper reviews the research progress of metabolic reprogramming of TAMs in HCC microenvironment.

References:

[1] SUNG H,FERLAY J,SIEGEL RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
[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.
[3] HEGDE PS,CHEN DS.Top 10 challenges in cancer immunotherapy[J].Immunity,2020,52(1):17-35.
[4] ZENG L,SU J,QIU W,et al.Survival outcomes and safety of programmed cell death/programmed cell death ligand 1 inhibitors for unresectable hepatocellular carcinoma:result from phase III trials[J].Cancer Control,2022,29:1389456324.
[5] ZHANG Q,HE Y,LUO N,et al.Landscape and dynamics of single immune cells in hepatocellular carcinoma[J].Cell,2019,179(4):829-845.
[6] HUANG Y,GE W,ZHOU J,et al.The role of tumor associated macrophages in hepatocellular carcinoma[J].J Cancer,2021,12(5):1284-1294.
[7] NETEA-MAIER RT,SMIT J,NETEA MG.Metabolic changes in tumor cells and tumor-associated macrophages:a mutual relationship[J].Cancer Lett,2018,413:102-109.
[8] SHAPOURI-MOGHADDAM A,MOHAMMADIAN S,VAZINI H,et al.Macrophage plasticity,polarization,and function in health and disease[J].J Cell Physiol,2018,233(9):6425-6440.
[9] MAZZONE M,MENGA A,CASTEGNA A.Metabolism and TAM functions-it takes two to tango[J].Febs J,2018,285(4):700-716.
[10] PAJAK B,SIWIAK E,SOLTYKA M,et al.2-deoxy-d-glucose and its analogs:from diagnostic to therapeutic agents[J].Int J Mol Sci,2019,21(1):234.
[11] SUN L,ZHOU F,SHAO Y,et al.Sedoheptulose kinase bridges the pentose phosphate pathway and immune responses in pathogen-challenged sea cucumber apostichopus japonicus[J].Dev Comp Immunol,2020,109:103694.
[12] PAN L,HU L,ZHANG L,et al.Deoxyelephantopin decreases the release of inflammatory cytokines in macrophage associated with attenuation of aerobic glycolysis via modulation of PKM2[J].Int Immunopharmacol,2020,79:106048.
[13] ZHANG T,ZHU X,WU H,et al.Targeting the ROS/PI3K/AKT/HIF-1alpha/HK2 axis of breast cancer cells:combined administration of polydatin and 2-deoxy-d-glucose[J].J Cell Mol Med,2019,23(5):3711-3723.
[14] ZHANG Z,DENG X,LIU Y,et al.PKM2,function and expression and regulation[J].Cell Biosci,2019,9:52.
[15] SHI Q,SHEN Q,LIU Y,et al.Increased glucose metabolism in TAMs fuels o-glcnacylation of lysosomal cathepsin B to promote cancer metastasis and chemoresistance[J].Cancer Cell,2022,40(10):1207-1222.
[16] XU D,WANG Y,WU J,et al.ECT2 overexpression promotes the polarization of tumor-associated macrophages in hepatocellular carcinoma via the ECT2/PLK1/PTEN pathway[J].Cell Death Dis,2021,12(2):162.
[17] NING WR,JIANG D,LIU XC,et al.Carbonic anhydrase XII mediates the survival and prometastatic functions of macrophages in human hepatocellular carcinoma[J].J Clin Invest,2022,132(7):e153110.
[18] WILLIAMS NC,O' NEILL L.A role for the krebs cycle intermediate citrate in metabolic reprogramming in innate immunity and inflammation[J].Front Immunol,2018,9:141.
[19] ZHU X,GUO Y,LIU Z,et al.Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS[J].Sci Rep,2021,11(1):18173.
[20] XU J,ZHENG Y,ZHAO Y,et al.Succinate/IL-1beta signaling axis promotes the inflammatory progression of endothelial and exacerbates atherosclerosis[J].Front Immunol,2022,13:817572.
[21] WU H,HAN Y,RODRIGUEZ SY,et al.Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages[J].Embo Mol Med,2019,11(11):e10698.
[22] ZHANG Q,WANG H,MAO C,et al.Fatty acid oxidation contributes to IL-1beta secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration[J].Mol Immunol,2018,94:27-35.
[23] LI Q,WANG C,WANG Y,et al.HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways[J].J Exp Clin Cancer Res,2018,37(1):231.
[24] ZAIDI NE,SHAZALI N,LEOW TC,et al.CD36-fatty acid-mediated metastasis via the bidirectional interactions of cancer cells and macrophages[J].Cells,2022,11(22):3556.
[25] SOUKUPOVA J,MALFETTONE A,BERTRAN E,et al.Epithelial-mesenchymal transition (EMT) induced by TGF-beta in hepatocellular carcinoma cells reprograms lipid metabolism[J].Int J Mol Sci,2021,22(11):5543.
[26] MORGAN MJ,KIM YS.Roles of RIPK3 in necroptosis,cell signaling,and disease[J].Exp Mol Med,2022,54(10):1695-1704.
[27] WU L,ZHANG X,ZHENG L,et al.RIPK3 orchestrates fatty acid metabolism in tumor-associated macrophages and hepatocarcinogenesis[J].Cancer Immunol Res,2020,8(5):710-721.
[28] BAI Y,YANG J,CUI Y,et al.Research progress of sirtuin4 in cancer[J].Front Oncol,2020,10:562950.
[29] LI Z,LI H,ZHAO ZB,et al.SIRT4 silencing in tumor-associated macrophages promotes HCC development via PPARdelta signalling-mediated alternative activation of macrophages[J].J Exp Clin Cancer Res,2019,38(1):469.
[30] KANG S,NAKANISHI Y,KIOI Y,et al.Semaphorin 6D reverse signaling controls macrophage lipid metabolism and anti-inflammatory polarization[J].Nat Immunol,2018,19(6):561-570.
[31] HASAN MN,CAPUK O,PATEL SM,et al.The role of metabolic plasticity of tumor-associated macrophages in shaping the tumor microenvironment immunity[J].Cancers (Basel),2022,14(14):3331.
[32] OH MH,SUN IH,ZHAO L,et al.Targeting glutamine metabolism enhances tumor-specific immunity by modulating suppressive myeloid cells[J].J Clin Invest,2020,130(7):3865-3884.
[33] ZHANG B,TANG B,GAO J,et al.A hypoxia-related signature for clinically predicting diagnosis,prognosis and immune microenvironment of hepatocellular carcinoma patients[J].J Transl Med,2020,18(1):342.
[34] BAILEY JD,DIOTALLEVI M,NICOL T,et al.Nitric oxide modulates metabolic remodeling in inflammatory macrophages through TCA cycle regulation and itaconate accumulation[J].Cell Rep,2019,28(1):218-230.
[35] MATOS A,CARVALHO M,BICHO M,et al.Arginine and arginases modulate metabolism,tumor microenvironment and prostate cancer progression[J].Nutrients,2021,13(12):4503.
[36] SHAN X,HU P,NI L,et al.Serine metabolism orchestrates macrophage polarization by regulating the IGF1-p38 axis[J].Cell Mol Immunol,2022,19(11):1263-1278.
[37] DONNE R,LUJAMBIO A.The liver cancer immune microenvironment:therapeutic implications for hepatocellular carcinoma[J].Hepatology,2023,77(5):1773-1796.
[38] MA Z,WANG LZ,CHENG JT,et al.Targeting hypoxia-inducible factor-1-mediated metastasis for cancer therapy[J].Antioxid Redox Signal,2021,34(18):1484-1497.
[39] WANG D,ZHANG X,LU Y,et al.Hypoxia inducible factor 1alpha in hepatocellular carcinoma with cirrhosis: association with prognosis[J].Pathol Res Pract,2018,214(12):1987-1992.
[40] ZHANG J,ZHANG Q,LOU Y,et al.Hypoxia-inducible factor-1alpha/interleukin-1beta signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment[J].Hepatology,2018,67(5):1872-1889.
[41] FLORES A,SANDOVAL-GONZALEZ S,TAKAHASHI R,et al.Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin[J].Nat Commun,2019,10(1):91.
[42] BALTAZAR F,AFONSO J,COSTA M,et al.Lactate beyond a waste metabolite:metabolic affairs and signaling in malignancy[J].Front Oncol,2020,10:231.
[43] CHEN P,ZUO H,XIONG H,et al.Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis[J].Proc Natl Acad Sci USA,2017,114(3):580-585.
[44] BOHN T,RAPP S,LUTHER N,et al.Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages[J].Nat Immunol,2018,19(12):1319-1329.
[45] BANTUG GR,GALLUZZI L,KROEMER G,et al.The spectrum of T cell metabolism in health and disease[J].Nat Rev Immunol,2018,18(1):19-34.
[46] GOSWAMI KK,BANERJEE S,BOSE A,et al.Lactic acid in alternative polarization and function of macrophages in tumor microenvironment[J].Hum Immunol,2022,83(5):409-417.
[47] WISSFELD J,WERNER A,YAN X,et al.Metabolic regulation of immune responses to cancer[J].Cancer Biol Med,2022,19(11):1528-1542.
[48] O' NEILL LA,KISHTON RJ,RATHMELL J.A guide to immunometabolism for immunologists[J].Nat Rev Immunol,2016,16(9):553-565.
[49] PACELLA I,PROCACCINI C,FOCACCETTI C,et al.Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth[J].Proc Natl Acad Sci USA,2018,115(28):E6546-E6555.
[50] CHEN DP,NING WR,JIANG ZZ,et al.Glycolytic activation of peritumoral monocytes fosters immune privilege via the PFKFB3-PD-L1 axis in human hepatocellular carcinoma[J].J Hepatol,2019,71(2):333-343.
[51] HARMON C,ROBINSON MW,HAND F,et al.Lactate-mediated acidification of tumor microenvironment induces apoptosis of liver-resident NK cells in colorectal liver metastasis[J].Cancer Immunol Res,2019,7(2):335-346.
[52] QUINN WR,JIAO J,TESLAA T,et al.Lactate limits T cell proliferation via the NAD(H) redox state[J].Cell Rep,2020,33(11):108500.
[53] GU J,ZHOU J,CHEN Q,et al.Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-beta signaling in regulatory T cells[J].Cell Rep,2022,39(12):110986.
[54] CHARBONNIER LM,CUI Y,STEPHEN-VICTOR E,et al.Functional reprogramming of regulatory T cells in the absence of Foxp3[J].Nat Immunol,2019,20(9):1208-1219.
[55] VITALE I,MANIC G,COUSSENS LM,et al.Macrophages and metabolism in the tumor microenvironment[J].Cell Metab,2019,30(1):36-50.
[56] LABADIE BW,BAO R,LUKE JJ.Reimagining IDO pathway inhibition in cancer immunotherapy via downstream focus on the tryptophan-kynurenine-aryl hydrocarbon axis[J].Clin Cancer Res,2019,25(5):1462-1471.
[57] SISKA PJ,JIAO J,MATOS C,et al.Kynurenine induces T cell fat catabolism and has limited suppressive effects in vivo[J].Ebiomedicine,2021,74:103734.
[58] CHEN CT,WU PH,HU CC,et al.Aberrant upregulation of indoleamine 2,3-dioxygenase 1 promotes proliferation and metastasis of hepatocellular carcinoma cells via coordinated activation of AhR and beta-catenin signaling[J].Int J Mol Sci,2021,22(21):11661.
[59] EGUCHI A,IWASA M.The role of elevated liver-type fatty acid-binding proteins in liver diseases[J].Pharm Res,2021,38(1):89-95.
[60] JIN R,HAO J,YI Y,et al.Regulation of macrophage functions by FABP-mediated inflammatory and metabolic pathways[J].Biochim Biophys Acta Mol Cell Biol Lipids,2021,1866(8):158964.
[61] NEUSCHAFER-RUBE F,SCHON T,KAHNT I,et al.LDL-dependent regulation of TNFalpha/PGE(2) induced COX-2/mPGES-1 expression in human macrophage cell lines[J].Inflammation,2023,46(3):893-911.
[62] LOFTUS RM,ASSMANN N,KEDIA-MEHTA N,et al.Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice[J].Nat Commun,2018,9(1):2341.
[63] GLASNER A,LEVI A,ENK J,et al.NKp46 receptor-mediated interferon-gamma production by natural killer cells increases fibronectin 1 to alter tumor architecture and control metastasis[J].Immunity,2018,48(1):107-119.
[64] KLAUSZ K,PEKAR L,BOJE AS,et al.Multifunctional NK cell-engaging antibodies targeting EGFR and NKp30 elicit efficient tumor cell killing and proinflammatory cytokine release[J].J Immunol,2022,209(9):1724-1735.
[65] XU Y,HAO X,REN Y,et al.Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma[J].Front Oncol,2022,12:1063423.
[66] FU C,JIANG A.Dendritic cells and CD8 T cell immunity in tumor microenvironment[J].Front Immunol,2018,9:3059.
[67] PENG X,HE Y,HUANG J,et al.Metabolism of dendritic cells in tumor microenvironment:for immunotherapy[J].Front Immunol,2021,12:613492.
[68] GROTH C,HU X,WEBER R,et al.Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression[J].Br J Cancer,2019,120(1):16-25.
[69] CASSETTA L,POLLARD JW.Targeting macrophages:therapeutic approaches in cancer[J].Nat Rev Drug Discov,2018,17(12):887-904.
[70] FAN N,ZHANG X,ZHAO W,et al.Covalent inhibition of pyruvate kinase M2 reprograms metabolic and inflammatory pathways in hepatic macrophages against non-alcoholic fatty liver disease[J].Int J Biol Sci,2022,18(14):5260-5275.
[71] KUDO M.Combination cancer immunotherapy in hepatocellular carcinoma[J].Liver Cancer,2018,7(1):20-27.
[72] TANG H,LIANG Y,ANDERS RA,et al.PD-L1 on host cells is essential for PD-L1 blockade-mediated tumor regression[J].J Clin Invest,2018,128(2):580-588.
[73] LU L G,ZHOU ZL,WANG XY,et al.PD-L1 blockade liberates intrinsic antitumourigenic properties of glycolytic macrophages in hepatocellular carcinoma[J].GUT,2022,71(12):2551-2560.
[74] SU P,WANG Q,BI E,et al.Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages[J].Cancer Res,2020,80(7):1438-1450.

Memo

Memo:
National Natural Science Foundation of China(No.82173830,81672800,82204259);国家自然科学基金(编号:82173830,81672800,82204259)
Last Update: 1900-01-01