Changes in metabolic processes are Blood sugar diet from enzymes involved in glycolysis. In Muscle soreness home remedies ror leukemia, carcinogenic signaling induces supporg stress, increases glucose uptake and aerobic glycolysis of activated T cells [ 91 ]. Dufort FJ, Gumina MR, Ta NL, Tao Y, Heyse SA, Scott DA, Richardson AD, Seyfried TN, Chiles TC Glucose-dependent de novo lipogenesis in B lymphocytes: a requirement for atp-citrate lyase in lipopolysaccharide-induced differentiation. Inhibition of glycolysis prevents differentiation into these pro-inflammatory subsets

Metabolic support for immune system -

Sci Adv. Wang Y, Hwang JY, Park HB, Yadav D, Oda T, Jin JO. Porphyran isolated from Pyropia yezoensis inhibits lipopolysaccharide-induced activation of dendritic cells in mice. Carbohydr Polym. Kolb D, Kolishetti N, Surnar B, Sarkar S, Guin S, Shah AS, et al.

Metabolic Modulation of the Tumor Microenvironment Leads to Multiple Checkpoint Inhibition and Immune Cell Infiltration. ACS Nano. Palmer CS, Ostrowski M, Balderson B, Christian N, Crowe SM. Glucose metabolism regulates T cell activation, differentiation, and functions. Togo M, Yokobori T, Shimizu K, Handa T, Kaira K, Sano T, et al.

Br J Cancer. Acetate Promotes T Cell Effector Function during Glucose Restriction. Sukumar M, Roychoudhuri R, Restifo NP. Nutrient Competition: A New Axis of Tumor Immunosuppression. Singer K, Kastenberger M, Gottfried E, Hammerschmied CG, Buttner M, Aigner M, et al.

Int J Cancer. The Immune Consequences of Lactate in the Tumor Microenvironment. Adv Exp Med Biol. Kareva I. Stem Cells. Wei H, Guan JL. Pro-tumorigenic function of autophagy in mammary oncogenesis. Halestrap AP. The monocarboxylate transporter family—Structure and functional characterization.

IUBMB Life. Huang Z, Gan J, Long Z, Guo G, Shi X, Wang C, et al. Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection. Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, et al.

Inhibitory effect of tumor cell-derived lactic acid on human T cells. Goetze K, Walenta S, Ksiazkiewicz M, Kunz-Schughart LA, Mueller-Klieser W. Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release. Int J Oncol. CAS PubMed Google Scholar. Bhagat TD, Von Ahrens D, Dawlaty M, Zou Y, Baddour J, Achreja A, et al.

Lactate-mediated epigenetic reprogramming regulates formation of human pancreatic cancer-associated fibroblasts. Dodard G, Tata A, Erick TK, Jaime D, Miah SMS, Quatrini L, et al.

Inflammation-Induced Lactate Leads to Rapid Loss of Hepatic Tissue-Resident NK Cells. Xia C, Liu C, He Z, Cai Y, Chen J. J Exp Clin Cancer Res. Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, et al. LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells.

Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, et al. Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses. Liu N, Luo J, Kuang D, Xu S, Duan Y, Xia Y, et al.

Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2alpha-mediated tumor progression. J Clin Invest. Fan SJ, Kroeger B, Marie PP, Bridges EM, Mason JD, McCormick K, et al.

Glutamine deprivation alters the origin and function of cancer cell exosomes. EMBO J. Caiola E, Colombo M, Sestito G, Lupi M, Marabese M, Pastorelli R, et al. Glutaminase Inhibition on NSCLC Depends on Extracellular Alanine Exploitation. Cohen AS, Geng L, Zhao P, Fu A, Schulte ML, Graves-Deal R, et al.

Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer. Transl Oncol. Carr EL, Kelman A, Wu GS, Gopaul R, Senkevitch E, Aghvanyan A, et al.

J Immunol. Johnson MO, Wolf MM, Madden MZ, Andrejeva G, Sugiura A, Contreras DC, et al. Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism. Puschel F, Favaro F, Redondo-Pedraza J, Lucendo E, Iurlaro R, Marchetti S, et al.

Starvation and antimetabolic therapy promote cytokine release and recruitment of immune cells. Proc Natl Acad Sci U S A. Nabe S, Yamada T, Suzuki J, Toriyama K, Yasuoka T, Kuwahara M, et al.

Cancer Sci. Hildebrand D, Heeg K, Kubatzky KF. Pasteurella multocida Toxin Manipulates T Cell Differentiation. Front Microbiol. Chen X, Chen S, Yu D. Metabolic Reprogramming of Chemoresistant Cancer Cells and the Potential Significance of Metabolic Regulation in the Reversal of Cancer Chemoresistance.

Lagranha CJ, Senna SM, de Lima TM, Silva E, Doi SQ, Curi R, et al. Beneficial effect of glutamine on exercise-induced apoptosis of rat neutrophils. Med Sci Sports Exerc. Shah AM, Wang Z, Ma J. Glutamine Metabolism and Its Role in Immunity, a Comprehensive Review. Animals Basel. Leone RD, Zhao L, Englert JM, Sun IM, Oh MH, Sun IH, et al.

Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Martinez-Colon GJ, Moore BB.

Prostaglandin E2 as a Regulator of Immunity to Pathogens. Kalinski P. Regulation of immune responses by prostaglandin E2. Zhang X, Yan K, Deng L, Liang J, Liang H, Feng D, et al.

Cell Transplant. Prostaglandin E 2 constrains systemic inflammation through an innate lymphoid cell-IL axis. Lu W, Yu W, He J, Liu W, Yang J, Lin X, et al. Reprogramming immunosuppressive myeloid cells facilitates immunotherapy for colorectal cancer.

EMBO Mol Med. Prostaglandin E2 As a Modulator of Viral Infections. Front Physiol. Luan B, Yoon YS, Le Lay J, Kaestner KH, Hedrick S, Montminy M.

CREB pathway links PGE2 signaling with macrophage polarization. Zelenay S, van der Veen AG, Bottcher JP, Snelgrove KJ, Rogers N, Acton SE, et al. Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity Cell.

Tang T, Scambler TE, Smallie T, Cunliffe HE, Ross EA, Rosner DR, et al. Macrophage responses to lipopolysaccharide are modulated by a feedback loop involving prostaglandin E2, dual specificity phosphatase 1 and tristetraprolin.

Bottcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, et al. NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control.

Saha J, Sarkar D, Pramanik A, Mahanti K, Adhikary A, Bhattacharyya S. PGE2-HIF1alpha reciprocal induction regulates migration, phenotypic alteration and immunosuppressive capacity of macrophages in tumor microenvironment.

Life Sci. Take Y, Koizumi S, Nagahisa A. Prostaglandin E. Receptor 4 Antagonist in Cancer Immunotherapy: Mechanisms of Action. Hansen M, Andersen MH. The role of dendritic cells in cancer.

Semin Immunopathol. Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol. Davel LE, Jasnis MA, de la Torre E, Gotoh T, Diament M, Magenta G, et al. Arginine metabolic pathways involved in the modulation of tumor-induced angiogenesis by macrophages.

FEBS Lett. Phillips MM, Sheaff MT, Szlosarek PW. Targeting arginine-dependent cancers with arginine-degrading enzymes: opportunities and challenges. Cancer Res Treat. Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y, Fuhrer T, et al. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.

Grohmann U, Mondanelli G, Belladonna ML, Orabona C, Pallotta MT, Iacono A, et al. Amino-acid sensing and degrading pathways in immune regulation. Cytokine Growth Factor Rev.

Liu H, Shen Z, Wang Z, Wang X, Zhang H, Qin J, et al. Increased expression of IDO associates with poor postoperative clinical outcome of patients with gastric adenocarcinoma. Yen MC, Lin CC, Chen YL, Huang SS, Yang HJ, Chang CP, et al. A novel cancer therapy by skin delivery of indoleamine 2,3-dioxygenase siRNA.

Clin Cancer Res. Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming. Currie E, Schulze A, Zechner R, Walther TC, Farese RV. Cellular fatty acid metabolism and cancer. Yadav UP, Singh T, Kumar P, Sharma P, Kaur H, Sharma S, et al.

Metabolic Adaptations in Cancer Stem Cells. Front Oncol. Li HY, Appelbaum FR, Willman CL, Zager RA, Banker DE. Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses.

Perrone F, Minari R, Bersanelli M, Bordi P, Tiseo M, Favari E, et al. The Prognostic Role of High Blood Cholesterol in Advanced Cancer Patients Treated With Immune Checkpoint Inhibitors.

J Immunother. Phelps CC, Vadia S, Boyaka PN, Varikuti S, Attia Z, Dubey P, et al. A listeriolysin O subunit vaccine is protective against Listeria monocytogenes. Nazih H, Bard JM. Oxysterols and LXRs in Breast Cancer Pathophysiology. Int J Mol Sci. Bjorkhem I. Are side-chain oxidized oxysterols regulators also in vivo?

J Lipid Res. Wu Q, Ishikawa T, Sirianni R, Tang H, McDonald JG, Yuhanna IS, et al. Raccosta L, Fontana R, Maggioni D, Lanterna C, Villablanca EJ, Paniccia A, et al.

The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils. J Exp Med. Baek AE, Yu YA, He S, Wardell SE, Chang CY, Kwon S, et al. The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Quist SR, Kraas L.

Treatment options for pyoderma gangrenosum. J Dtsch Dermatol Ges. PubMed Google Scholar. Jia Y, Yang Q, Wang Y, Li W, Chen X, Xu T, et al.

Hyperactive PI3Kdelta predisposes naive T cells to activation via aerobic glycolysis programs. Cell Mol Immunol. Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma. Wolf T, Jin W, Zoppi G, Vogel IA, Akhmedov M, Bleck CKE, et al.

Dynamics in protein translation sustaining T cell preparedness. Nat Immunol. Filipek A, Mikolajczyk TP, Guzik TJ, Naruszewicz M. Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy Against Early and Advanced Atherosclerotic Lesions.

Pharmaceuticals Basel. Theodoraki MN, Hoffmann TK, Jackson EK, Whiteside TL. Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune competence. Clin Exp Immunol. Masui K, Harachi M, Cavenee WK, Mischel PS, Shibata N.

mTOR complex 2 is an integrator of cancer metabolism and epigenetics. Zhang X, Liang T, Yang W, Zhang L, Wu S, Yan C, et al. Astragalus membranaceus Injection Suppresses Production of Interleukin-6 by Activating Autophagy through the AMPK-mTOR Pathway in Lipopolysaccharide-Stimulated Macrophages.

Oxid Med Cell Longev. PubMed PubMed Central Google Scholar. Sato R, Kato A, Chimura T, Saitoh SI, Shibata T, Murakami Y, et al. Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.

Kim YK, Chae SC, Yang HJ, An DE, Lee S, Yeo MG, et al. Immune Netw. Salminen A, Kauppinen A, Kaarniranta K. AMPK activation inhibits the functions of myeloid-derived suppressor cells MDSC : impact on cancer and aging.

J Mol Med Berl. Wang S, Lin Y, Xiong X, Wang L, Guo Y, Chen Y, et al. Low-dose metformin reprograms the tumor immune microenvironment in human esophageal cancer: Results of a phase II clinical trial. Zhu YP, Brown JR, Sag D, Zhang L, Suttles J.

Csoka B, Selmeczy Z, Koscso B, Nemeth ZH, Pacher P, Murray PJ, et al. Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J. Zhi X, Wang Y, Zhou X, Yu J, Jian R, Tang S, et al. RNAi-mediated CD73 suppression induces apoptosis and cell-cycle arrest in human breast cancer cells.

Amirani E, Hallajzadeh J, Asemi Z, Mansournia MA, Yousefi B. Effects of chitosan and oligochitosans on the phosphatidylinositol 3-kinase-AKT pathway in cancer therapy. Int J Biol Macromol. Kim J, Yang GS, Lyon D, Kelly DL, Stechmiller J. Metabolomics: Impact of comorbidities and inflammation on sickness behaviors for individuals with chronic wounds.

Adv Wound Care New Rochelle. Sohrabi Y, Lagache SMM, Voges VC, Semo D, Sonntag G, Hanemann I, et al. OxLDL-mediated immunologic memory in endothelial cells. J Mol Cell Cardiol. Sun L, Yang X, Yuan Z, Wang H. Metabolic Reprogramming in Immune Response and Tissue Inflammation. Arterioscler Thromb Vasc Biol.

Wei F, Wang D, Wei J, Tang N, Tang L, Xiong F, et al. Metabolic crosstalk in the tumor microenvironment regulates antitumor immunosuppression and immunotherapy resisitance. Cell Mol Life Sci. Tan SY, Kelkar Y, Hadjipanayis A, Shipstone A, Wynn TA, Hall JP.

Gardiner CM. NK cell metabolism. Takeshima Y, Iwasaki Y, Fujio K, Yamamoto K. Metabolism as a key regulator in the pathogenesis of systemic lupus erythematosus. Semin Arthritis Rheum. Shin B, Benavides GA, Geng J, Koralov SB, Hu H, Darley-Usmar VM, et al. Mitochondrial Oxidative Phosphorylation Regulates the Fate Decision between Pathogenic Th17 and Regulatory T Cells.

Lu H, Liu F, Li Y, Wang J, Ma M, Gao J, et al. Chromatin accessibility of CD8 T cell differentiation and metabolic regulation.

Cell Biol Toxicol. Van den Bossche J, van der Windt GJW. Fatty Acid Oxidation in Macrophages and T Cells: Time for Reassessment? Article PubMed CAS Google Scholar. Saibil SD, St Paul M, Laister RC, Garcia-Batres CR, Israni-Winger K, Elford AR, et al. Activation of Peroxisome Proliferator-Activated Receptors alpha and delta Synergizes with Inflammatory Signals to Enhance Adoptive Cell Therapy.

Cancer Res. Zhang C, Yue C, Herrmann A, Song J, Egelston C, Wang T, et al. Ghergurovich JM, Garcia-Canaveras JC, Wang J, Schmidt E, Zhang Z, TeSlaa T, et al. A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway.

Nat Chem Biol. Michaeloudes C, Bhavsar PK, Mumby S, Xu B, Hui CKM, Chung KF, et al. Role of Metabolic Reprogramming in Pulmonary Innate Immunity and Its Impact on Lung Diseases. J Innate Immun. Kumar S, Dikshit M. Metabolic Insight of Neutrophils in Health and Disease.

Kumar R, Singh P, Kolloli A, Shi L, Bushkin Y, Tyagi S, et al. Immunometabolism of Phagocytes During Mycobacterium tuberculosis Infection. Front Mol Biosci.

Wang S, Liu F, Tan KS, Ser HL, Tan LT, Lee LH, et al. Effect of R -salbutamol on the switch of phenotype and metabolic pattern in LPS-induced macrophage cells. J Cell Mol Med. Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation.

Wang Z, Guan D, Wang S, Chai LYA, Xu S, Lam KP. Glycolysis and Oxidative Phosphorylation Play Critical Roles in Natural Killer Cell Receptor-Mediated Natural Killer Cell Functions. Li Y, Wang T, Hu X, Zhang H, Chen L, Bao X, et al.

Study of KIR gene expression at the mRNA level in specific donor-derived NK cells after allogeneic HSCT. Neagu M. Metabolic Traits in Cutaneous Melanoma. Nielsen M, Krarup-Hansen A, Hovgaard D, Petersen MM, Loya AC, Westergaard MCW, et al.

Cancer Immunol Immunother. Zhang D, Jin W, Wu R, Li J, Park SA, Tu E, et al. High Glucose Intake Exacerbates Autoimmunity through Reactive-Oxygen-Species-Mediated TGF-beta Cytokine Activation. Lawless SJ, Kedia-Mehta N, Walls JF, McGarrigle R, Convery O, Sinclair LV, et al.

Glucose represses dendritic cell-induced T cell responses. Balyan R, Gund R, Ebenezer C, Khalsa JK, Verghese DA, Krishnamurthy T, et al. Modulation of Naive CD8 T Cell Response Features by Ligand Density, Affinity, and Continued Signaling via Internalized TCRs.

Newsholme P, Gordon S, Newsholme EA. Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. Biochem J. Oronsky BT, Oronsky N, Fanger GR, Parker CW, Caroen SZ, Lybeck M, et al.

Follow the ATP: tumor energy production: a perspective. Anticancer Agents Med Chem. Bours MJ, Swennen EL, Di Virgilio F, Cronstein BN, Dagnelie PC. Killeen ME, Ferris L, Kupetsky EA, Falo L Jr, Mathers AR. Signaling through purinergic receptors for ATP induces human cutaneous innate and adaptive Th17 responses: implications in the pathogenesis of psoriasis.

Schenk U, Frascoli M, Proietti M, Geffers R, Traggiai E, Buer J, et al. ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. Sci Signal. Aral K, Milward MR, Gupta D, Cooper PR. Effects of Porphyromonas gingivalis and Fusobacterium nucleatum on inflammasomes and their regulators in H cells.

Mol Oral Microbiol. De Marchi E, Orioli E, Pegoraro A, Sangaletti S, Portararo P, Curti A, et al. Trabanelli S, Ocadlikova D, Gulinelli S, Curti A, Salvestrini V, Vieira RP, et al. Sousa JB, Diniz C. The Adenosinergic System as a Therapeutic Target in the Vasculature: New Ligands and Challenges.

den Hartigh LJ, Connolly-Rohrbach JE, Fore S, Huser TR, Rutledge JC. Fatty acids from very low-density lipoprotein lipolysis products induce lipid droplet accumulation in human monocytes.

Article Google Scholar. Ecker J, Liebisch G, Englmaier M, Grandl M, Robenek H, Schmitz G. Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes. Freigang S, Ampenberger F, Weiss A, Kanneganti TD, Iwakura Y, Hersberger M, et al.

Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1alpha and sterile vascular inflammation in atherosclerosis. Amersfoort J, Schaftenaar FH, Douna H, van Santbrink PJ, van Puijvelde GHM, Slutter B, et al. Diet-induced dyslipidemia induces metabolic and migratory adaptations in regulatory T cells.

Cardiovasc Res. Robertson EC, Tisdall FF. Diet and Nutrition: Nutrition and Resistance to Disease. Can Med Assoc J. CAS PubMed PubMed Central Google Scholar. Nielsen JP, Foged NT, Sorensen V, Barfod K, Bording A, Petersen SK. Vaccination against progressive atrophic rhinitis with a recombinant Pasteurella multocida toxin derivative.

Can J Vet Res. Eleftheriadis T, Pissas G, Liakopoulos V, Stefanidis I. Int J Mol Med. Yaqoob P, Calder PC. Glutamine requirement of proliferating T lymphocytes.

Kagoya Y, Tanaka S, Guo T, Anczurowski M, Wang CH, Saso K, et al. A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects. Nat Med. Coeffier M, Miralles-Barrachina O, Le Pessot F, Lalaude O, Daveau M, Lavoinne A, et al.

Influence of glutamine on cytokine production by human gut in vitro. Ghosh T, Barik S, Bhuniya A, Dhar J, Dasgupta S, Ghosh S, et al.

Tumor-associated mesenchymal stem cells inhibit naive T cell expansion by blocking cysteine export from dendritic cells. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. Sido B, Braunstein J, Breitkreutz R, Herfarth C, Meuer SC.

Thiol-mediated redox regulation of intestinal lamina propria T lymphocytes. Han F, Pang X, Wang Q, Liu Y, Liu L, Chai Y, et al. Dietary Serine and Sulfate-Containing Amino Acids Related to the Nutritional Status of Selenium in Lactating Chinese Women.

Biol Trace Elem Res. Behringer S, Wingert V, Oria V, Schumann A, Grunert S, Cieslar-Pobuda A, et al. Targeted Metabolic Profiling of Methionine Cycle Metabolites and Redox Thiol Pools in Mammalian Plasma, Cells and Urine. Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, et al.

mTOR regulates memory CD8 T-cell differentiation. PI3K orchestration of the in vivo persistence of chimeric antigen receptor-modified T cells. Kawalekar OU, RS OC, Fraietta JA, Guo L, McGettigan SE, Posey AD Jr, et al.

Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, et al. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics.

Zhang L, Tschumi BO, Lopez-Mejia IC, Oberle SG, Meyer M, Samson G, et al. Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner. Guri Y, Nordmann TM, Roszik J. mTOR at the Transmitting and Receiving Ends in Tumor Immunity.

Ventura-Aguiar P, Campistol JM, Diekmann F. Safety of mTOR inhibitors in adult solid organ transplantation. Expert Opin Drug Saf. Pollizzi KN, Patel CH, Sun IH, Oh MH, Waickman AT, Wen J, et al. Karthikeyan S, Geschwind JF, Ganapathy-Kanniappan S. Tumor cells and memory T cells converge at glycolysis: therapeutic implications.

Cancer Biol Ther. Sukumar M, Liu J, Ji Y, Subramanian M, Crompton JG, Yu Z, et al. Zhang Y, Kurupati R, Liu L, Zhou XY, Zhang G, Hudaihed A, et al. Download references.

This work was supported in part by grants from the following sources: the National Natural Science Foundation of China , , the Natural Science Foundation of Hunan Province JJ, JJ, JJ JJ , the Research Project of Health Commission of Hunan Province , B, B , Ascend Foundation of National cancer center NCCb68 , and Supported By Hunan Cancer Hospital Climb Plan ZX, YF Hunan Key Laboratory of Cancer Metabolism, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Tongzipo Road, , Changsha, Hunan, China.

University of South China, , Hengyang, Hunan, China. You can also search for this author in PubMed Google Scholar. XLZ and OYLD contributed to drafting and editing of the manuscript, shared the first authorship.

LQJ and ZYJ designed, revised and finalized the manuscript. LJG, TSM, HYQ and WNYY participated in the drafting and editing manuscript. YP, TL, PQ, and RS participated in the revision and coordination.

LJX, TYY, LX and YYQ contributed to literature search. SM, SYR, WH participated in the conception and coordination. All authors contributed toward data analysis, drafting and revising the paper and agreed to be accountable for all aspects of the work.

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Mol Cancer 20 , 28 Download citation. Received : 19 October Accepted : 15 January Published : 05 February Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer.

Introduction Metabolism involves a network of biochemical reactions that convert nutrients into small molecules called metabolites [ 1 ]. Main text Overview of metabolism of tumor cells and immune cells 1. Metabolism of tumor cells Energy metabolism reprogramming, which fuels fast cell growth and proliferation by adjustments of energy metabolism, has been considered as an emerging hallmark of cancer [ 4 ].

Full size image. Table 1 Different metabolic ways of immune cells Full size table. Competition for nutrients between tumor cells and immune cells Metabolic transitions are not unique to cancer cells, but are also characteristic of other rapidly proliferating cells, such as activated T cells, Treg cell, neutrophils and so on [ 28 ].

Effect of tumor metabolic reprogramming on immune cells In addition to nutrient consumption, metabolites produced by cancer cells can have a profound effect on immune cells in the microenvironment [ 57 ]. The effect of tumor metabolites on immune cell Lactate The aberrant glycolysis of tumor means that tumor cells consume a lot of glucose and produce large amount of lactic acid even in the presence of sufficient oxygen, with a correspondingly low rate of OXPHOS.

Glutamine Glutamine metabolism as a whole is a crucial element of cancer cell metabolism. PGE 2 Arachidonic acid is an important class of eicosapentaenoic acid related to essential fatty acids in tumor cells, and it is an important substrate for the synthesis of prostaglandins.

Arginine Most tumor cells lack ASS1 argininosuccinate synthetase 1 , a key enzyme that produces arginine, and therefore will cause the loss of intracellular arginine synthesis capacity [ 95 ].

Tryptophan Tryptophan is an essential amino acid necessary for organisms to carry out protein synthesis and other life metabolic activities. Fatty acids Tumor cells often have increased rates of de novo fatty acid synthesis to divert energy production into anabolic pathways for the generation of plasma membrane phospholipids and signaling molecules.

Cholesterol Cholesterol is an important part of the surface of the cell membrane. The regulation of metabolites produced by tumor cells in immune cells The metabolites are known regulators of immune cell function, such as lactate, fatty acid, PGE 2 and arginine, etc.

Effect of immune cell metabolic reprogramming on tumor immunity The activated process of immune cell requires a large amount of energy and metabolic intermediates to meet the needs of biosynthesis, so as to complete the proliferation, differentiation and execution of effector functions. Effect of immune cell metabolic pattern on immune cell functions.

Table 2 Metabolic changing of immune cells Full size table. Metabolic interventions in tumor immunity A better understanding of the processes inducing metabolic interventions in cancer cell and immune cell might also reveal new therapeutic targets.

Availability of data and materials Not applicable. Abbreviations OXPHOS: Mitochondrial oxidative phosphorylation ATP: Adenosine triphosphate PPP: Pentose phosphate pathway TCA cycle: Tricarboxylic acid cycle DCs: Dendritic cells Teff: Effector T cell Treg: Regulatory T cells FAO: Fatty acid oxidation TIL: Tumor-infiltrating lymphocytes TME: Tumor microenvironment AMPK: AMP-activated protein kinase Tm: Memory T cell ARG: Arginase NOS: Nitric oxide synthase HK2: Hexokinase 2 PFK1: Phosphofructokinase 1 PKM2: Pyruvate kinases type M2 ICIs: Immune checkpoint inhibitors TCR: T cell receptor IL Interleukin References Rodriguez C, Puente-Moncada N, Reiter RJ, Sanchez-Sanchez AM, Herrera F, Rodriguez-Blanco J, et al.

Article CAS PubMed PubMed Central Google Scholar Lapa B, Goncalves AC, Jorge J, Alves R, Pires AS, Abrantes AM, et al. Article CAS PubMed Google Scholar Callao V, Montoya E. Article CAS PubMed Google Scholar Zhang J, Yang J, Lin C, Liu W, Huo Y, Yang M, et al.

Article CAS PubMed PubMed Central Google Scholar Dominski A, Krawczyk M, Konieczny T, Kasprow M, Forys A, Pastuch-Gawolek G, et al. Article CAS PubMed Google Scholar Cicco S, Cicco G, Racanelli V, Vacca A. Article PubMed PubMed Central CAS Google Scholar Terry S, Engelsen AST, Buart S, Elsayed WS, Venkatesh GH, Chouaib S.

Article PubMed Google Scholar Chen B, Gao A, Tu B, Wang Y, Yu X, Wang Y, et al. Article CAS PubMed Google Scholar Karayama M, Masuda J, Mori K, Yasui H, Hozumi H, Suzuki Y, et al.

Article CAS PubMed PubMed Central Google Scholar Ramapriyan R, Caetano MS, Barsoumian HB, Mafra ACP, Zambalde EP, Menon H, et al. Article CAS PubMed Google Scholar Cronin SJF, Seehus C, Weidinger A, Talbot S, Reissig S, Seifert M, et al. Article CAS PubMed PubMed Central Google Scholar Moon JY, Zolnik CP, Wang Z, Qiu Y, Usyk M, Wang T, et al.

Article PubMed PubMed Central Google Scholar Oliveira LM, Teixeira FME, Sato MN. Article PubMed PubMed Central CAS Google Scholar Shyer JA, Flavell RA, Bailis W. Article CAS PubMed Google Scholar Sun L, Song L, Wan Q, Wu G, Li X, Wang Y, et al. Article CAS PubMed PubMed Central Google Scholar Schug ZT, Vande Voorde J, Gottlieb E.

Article CAS PubMed PubMed Central Google Scholar Schug ZT, Peck B, Jones DT, Zhang Q, Grosskurth S, Alam IS, et al. Article CAS PubMed PubMed Central Google Scholar Mashimo T, Pichumani K, Vemireddy V, Hatanpaa KJ, Singh DK, Sirasanagandla S, et al. Article CAS PubMed PubMed Central Google Scholar Huang, Li T, Wang L, Zhang L, Yan R, Li K, et al.

Article CAS Google Scholar Hao S, Yan KK, Ding L, Qian C, Chi H, Yu J. Article CAS Google Scholar Ghesquiere B, Wong BW, Kuchnio A, Carmeliet P. Article CAS PubMed Google Scholar Ricciardi S, Manfrini N, Alfieri R, Calamita P, Crosti MC, Gallo S, et al. Article CAS PubMed PubMed Central Google Scholar Pearce EL, Poffenberger MC, Chang CH, Jones RG.

Article PubMed PubMed Central CAS Google Scholar Tan S, Li S, Min Y, Gistera A, Moruzzi N, Zhang J, et al. Article CAS PubMed PubMed Central Google Scholar Wu H, Estrella V, Beatty M, Abrahams D, El-Kenawi A, Russell S, et al.

Article CAS PubMed PubMed Central Google Scholar Wu N, Chen D, Sun H, Tan J, Zhang Y, Zhang T, et al. Article CAS PubMed Google Scholar Saka D, Gokalp M, Piyade B, Cevik NC, Arik Sever E, Unutmaz D, et al.

Article CAS PubMed PubMed Central Google Scholar Dai X, Lu L, Deng S, Meng J, Wan C, Huang J, et al. Article CAS PubMed PubMed Central Google Scholar Qing J, Zhang Z, Novak P, Zhao G, Yin K. Article CAS PubMed Google Scholar da Silva CO, Gicquel T, Daniel Y, Bartholo T, Vene E, Loyer P, et al.

Article PubMed PubMed Central CAS Google Scholar Joshi MB, Ahamed R, Hegde M, Nair AS, Ramachandra L, Satyamoorthy K. Article CAS PubMed PubMed Central Google Scholar Wang Y, Hwang JY, Park HB, Yadav D, Oda T, Jin JO.

Article CAS PubMed Google Scholar Kolb D, Kolishetti N, Surnar B, Sarkar S, Guin S, Shah AS, et al. Article PubMed PubMed Central CAS Google Scholar Togo M, Yokobori T, Shimizu K, Handa T, Kaira K, Sano T, et al.

Article CAS PubMed PubMed Central Google Scholar Singer K, Kastenberger M, Gottfried E, Hammerschmied CG, Buttner M, Aigner M, et al.

Article PubMed Google Scholar Kareva I. Article PubMed Google Scholar Wei H, Guan JL. Article CAS PubMed PubMed Central Google Scholar Halestrap AP. Article CAS PubMed Google Scholar Huang Z, Gan J, Long Z, Guo G, Shi X, Wang C, et al. Article CAS PubMed Google Scholar Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, et al.

Article CAS PubMed Google Scholar Goetze K, Walenta S, Ksiazkiewicz M, Kunz-Schughart LA, Mueller-Klieser W. CAS PubMed Google Scholar Bhagat TD, Von Ahrens D, Dawlaty M, Zou Y, Baddour J, Achreja A, et al.

Article CAS PubMed PubMed Central Google Scholar Xia C, Liu C, He Z, Cai Y, Chen J. Article CAS PubMed PubMed Central Google Scholar Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, et al.

Article CAS PubMed Google Scholar Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, et al. Article CAS PubMed PubMed Central Google Scholar Liu N, Luo J, Kuang D, Xu S, Duan Y, Xia Y, et al.

Article PubMed PubMed Central Google Scholar Fan SJ, Kroeger B, Marie PP, Bridges EM, Mason JD, McCormick K, et al. Article PubMed PubMed Central Google Scholar Carr EL, Kelman A, Wu GS, Gopaul R, Senkevitch E, Aghvanyan A, et al.

Article CAS PubMed Google Scholar Johnson MO, Wolf MM, Madden MZ, Andrejeva G, Sugiura A, Contreras DC, et al. Article CAS PubMed PubMed Central Google Scholar Nabe S, Yamada T, Suzuki J, Toriyama K, Yasuoka T, Kuwahara M, et al.

Article CAS PubMed PubMed Central Google Scholar Hildebrand D, Heeg K, Kubatzky KF. Article PubMed PubMed Central Google Scholar Chen X, Chen S, Yu D. Article CAS PubMed Google Scholar Shah AM, Wang Z, Ma J. Article CAS PubMed PubMed Central Google Scholar Martinez-Colon GJ, Moore BB. Article CAS PubMed Google Scholar Kalinski P.

Article CAS PubMed Google Scholar Zhang X, Yan K, Deng L, Liang J, Liang H, Feng D, et al. Article CAS PubMed PubMed Central Google Scholar Lu W, Yu W, He J, Liu W, Yang J, Lin X, et al. Article PubMed PubMed Central Google Scholar Luan B, Yoon YS, Le Lay J, Kaestner KH, Hedrick S, Montminy M.

Article CAS PubMed PubMed Central Google Scholar Zelenay S, van der Veen AG, Bottcher JP, Snelgrove KJ, Rogers N, Acton SE, et al.

CAS PubMed Google Scholar Tang T, Scambler TE, Smallie T, Cunliffe HE, Ross EA, Rosner DR, et al. Article PubMed PubMed Central CAS Google Scholar Bottcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, et al.

Article CAS Google Scholar Saha J, Sarkar D, Pramanik A, Mahanti K, Adhikary A, Bhattacharyya S. Article CAS PubMed Google Scholar Take Y, Koizumi S, Nagahisa A.

Article CAS PubMed PubMed Central Google Scholar Hansen M, Andersen MH. Article CAS PubMed Google Scholar Bronte V, Zanovello P.

Article CAS PubMed Google Scholar Davel LE, Jasnis MA, de la Torre E, Gotoh T, Diament M, Magenta G, et al. Article CAS PubMed Google Scholar Phillips MM, Sheaff MT, Szlosarek PW.

Article PubMed PubMed Central Google Scholar Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y, Fuhrer T, et al. Article CAS PubMed PubMed Central Google Scholar Grohmann U, Mondanelli G, Belladonna ML, Orabona C, Pallotta MT, Iacono A, et al.

Article CAS PubMed Google Scholar Liu H, Shen Z, Wang Z, Wang X, Zhang H, Qin J, et al. Article CAS PubMed PubMed Central Google Scholar Yen MC, Lin CC, Chen YL, Huang SS, Yang HJ, Chang CP, et al. Article CAS PubMed PubMed Central Google Scholar Currie E, Schulze A, Zechner R, Walther TC, Farese RV.

Article CAS PubMed PubMed Central Google Scholar Yadav UP, Singh T, Kumar P, Sharma P, Kaur H, Sharma S, et al. Article PubMed PubMed Central Google Scholar Li HY, Appelbaum FR, Willman CL, Zager RA, Banker DE.

Article CAS PubMed Google Scholar Perrone F, Minari R, Bersanelli M, Bordi P, Tiseo M, Favari E, et al. Article CAS PubMed Google Scholar Phelps CC, Vadia S, Boyaka PN, Varikuti S, Attia Z, Dubey P, et al. Article CAS PubMed PubMed Central Google Scholar Raccosta L, Fontana R, Maggioni D, Lanterna C, Villablanca EJ, Paniccia A, et al.

Article CAS PubMed PubMed Central Google Scholar Baek AE, Yu YA, He S, Wardell SE, Chang CY, Kwon S, et al.

Article PubMed PubMed Central CAS Google Scholar Quist SR, Kraas L. PubMed Google Scholar Jia Y, Yang Q, Wang Y, Li W, Chen X, Xu T, et al. Article CAS PubMed PubMed Central Google Scholar Wolf T, Jin W, Zoppi G, Vogel IA, Akhmedov M, Bleck CKE, et al.

Article CAS PubMed PubMed Central Google Scholar Filipek A, Mikolajczyk TP, Guzik TJ, Naruszewicz M. Article CAS PubMed Google Scholar Masui K, Harachi M, Cavenee WK, Mischel PS, Shibata N.

Article CAS PubMed Google Scholar Zhang X, Liang T, Yang W, Zhang L, Wu S, Yan C, et al. PubMed PubMed Central Google Scholar Sato R, Kato A, Chimura T, Saitoh SI, Shibata T, Murakami Y, et al. Article CAS PubMed Google Scholar Kim YK, Chae SC, Yang HJ, An DE, Lee S, Yeo MG, et al.

Article PubMed PubMed Central Google Scholar Salminen A, Kauppinen A, Kaarniranta K. Article CAS Google Scholar Wang S, Lin Y, Xiong X, Wang L, Guo Y, Chen Y, et al.

Article CAS PubMed Google Scholar Csoka B, Selmeczy Z, Koscso B, Nemeth ZH, Pacher P, Murray PJ, et al. Article CAS PubMed PubMed Central Google Scholar Zhi X, Wang Y, Zhou X, Yu J, Jian R, Tang S, et al.

Article CAS PubMed Google Scholar Amirani E, Hallajzadeh J, Asemi Z, Mansournia MA, Yousefi B. Article CAS PubMed Google Scholar Kim J, Yang GS, Lyon D, Kelly DL, Stechmiller J.

Article CAS PubMed Google Scholar Takeshima Y, Iwasaki Y, Fujio K, Yamamoto K. Article CAS PubMed Google Scholar Shin B, Benavides GA, Geng J, Koralov SB, Hu H, Darley-Usmar VM, et al.

Article CAS PubMed PubMed Central Google Scholar Lu H, Liu F, Li Y, Wang J, Ma M, Gao J, et al. Article PubMed CAS Google Scholar Saibil SD, St Paul M, Laister RC, Garcia-Batres CR, Israni-Winger K, Elford AR, et al.

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Normal bone Metabolic support for immune system Xupport homeostasis ensures consistent production of progenitor cells and Metabolic support for immune system blood cells. Suppott requires Non-GMO sauces reliable immmune of nutrients in Anti-angiogenesis therapy for solid tumors free fatty acids, carbohydrates sjpport protein. Furthermore, rapid Muscle soreness home remedies Mwtabolic occur in response to stress such immunf infection which can alter the demand for each of these metabolites. In response to infection the haematopoietic stem cells HSCs must respond and expand rapidly to facilitate the process of emergency granulopoiesis required for the immediate immune response. This involves a shift from the use of glycolysis to oxidative phosphorylation for energy production and therefore an increased demand for metabolites. Thus, the right balance of each dietary component helps to maintain not only normal homeostasis but also the ability to quickly respond to systemic stress.

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Immune and non-immune functions of adipose tissue leukocytes. Marchingo JM, Cantrell DA. Protein synthesis, degradation, and energy meta bolism in T cell immunity. Cell Mol Immunol. Heintzman DR, Fisher EL, Rathmell JC.

Microenvironmental Inflfluences on T Cell Immunity in Cancer and Inflflammation. Lee MS, Bensinger SJ. Reprogramming cholesterol metabolism in macrophages and its role in host defense against cholesterol-dependent cytolysins. Chou WC, Rampanelli E, Li X, Ting JP.

Impact of intracellular innate immune receptors on immunometabolism. Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC, Plas DR, et al. The CD28 signaling pathway regulates glucose metabolism.

Bian Y, Li W, Kremer DM, Sajjakulnukit P, Li S, Crespo J, et al. Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. Reinfeld BI, Madden MZ, Wolf MM, Chytil A, Bader JE, Patterson AR, et al. Cell-programmed nutrient partitioning in the tumour microenvironment.

Long L, Wei J, Lim SA, Raynor JL, Shi H, Connelly JP, et al. CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity. Huang H, Zhou P, Wei J, Long L, Shi H, Dhungana Y, et al. Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.

Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, et al. J Immunol. Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, et al. HIF1a-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells.

J Exp Med. Boothby MR, Brookens SK, Raybuck AL, Cho SH. Supplying the trip to antibody production-nutrients, signaling, and the programming of cellular metabolism in the mature B lineage.

Moller SH, Wang L, Ho PC. Metabolic programming in dendritic cells tailors immune responses and homeostasis. Article Google Scholar. Wculek SK, Dunphy G, Heras-Murillo I, Mastrangelo A, Sancho D.

Metabolism of tissue macrophages in homeostasis and pathology. Purohit V, Wagner A, Yosef N, Kuchroo VK. Systems approaches to study immunometabolism. Man K, Kallies A, Vasanthakumar A. Resident and migratory adipose immune cells control systemic metabolism and thermogenesis.

Prendeville H, Lynch L. Diet, lipids, and antitumor immunity. Download references. The author acknowledges N. Chapman and H. Shi for scientific discussion and critical reading of the paper. Department of Immunology, St.

You can also search for this author in PubMed Google Scholar. Correspondence to Hongbo Chi. Reprints and permissions. Chi, H. Immunometabolism at the intersection of metabolic signaling, cell fate, and systems immunology. Cell Mol Immunol 19 , — Download citation.

Received : 17 January Accepted : 18 January Published : 21 February Issue Date : March Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content Thank you for visiting nature. Download PDF. Subjects Cancer metabolism Cancer microenvironment. Full size image.

Pathways: bidirectional metabolic signaling in innate and adaptive immunity Cells in the innate and adaptive immune systems are characterized by rapid transition between the quiescent and activated states, marked heterogeneity of cell fate choices, and context-specific tissue adaptation.

Cells: metabolic control of immune cell state and fate With the increasing understanding of metabolic signaling, its impacts on immune cell activation state and fate decision are also recognized. Systems: integrating intracellular network, intercellular crosstalk, and organismal immunometabolism One main challenge of studying metabolic pathways is their complexity, which stems from the vast number of metabolites, the diverse chemical structures, and the sophisticated regulation of the enzymes that control them.

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Select options SPIRULINA — Equine immune support, amino acids, coat and skin, muscles, liver, lungs, kidney, insect bites, metabolism. GC B cells showed that mTORC1 activation and c-MYC accumulation were increased, and genes related to glycolysis were also up-regulated [ 81 ].

Due to the increased protein expression of glycolysis, TCA cycle and ETC in these cells, the number of mitochondria and the expression of HIF1α also increased [ 82 ].

Compared with the naive B cells, plasma cells have a higher protein synthesis rate, absorb more amino acids and glucose, and produce a large number of ROS [ 83 ].

In activated B cells, the decrease of oxygen concentration reduces mTORC1 signal transduction and inhibits the conversion of immunoglobulins isoforms [ 77 ]. However, hypoxia promotes plasma cell survival and supports regulatory B cell function. Hypoxia promotes the expression of HIF1α [ 77 , 83 ], triggers steady transcription and regulates the expression of glucose transporters and glycolytic enzymes when oxygen concentration is limited [ 77 ].

With the participation of BCR or IL-4 stimulation, activated B cells became larger, total protein and CD expression increased [ 84 ]. In addition, BCR signaling pathway increases Glut1 expression and glucose uptake in PI3K-dependent mechanisms [ 85 ] Table 2.

B cells transit from static state and recycling to activation, proliferate rapidly, and produce a large number of antibodies. Only when metabolism, extracellular stimulation and intracellular signal transduction work together, the humoral response dominated by B cells can be successfully carried out.

Breaking this balance will lead to malignant transformation of B cells. Therefore, the discovery of metabolic differences between B cell activation and malignant tumors is very important for the treatment and prevention of B cell lymphoma.

Nowadays, studies on immune cells and metabolism have received extensive attention. Immune cells are involved in the progression of many human diseases, such as cancer [ 86 , 87 , 88 ], autoimmune diseases [ 89 ], and heart disease [ 90 ].

The metabolic pathways of sugar, fat and amino acids interact with each other, which are closely related to the survival and activation of immune cells. Studies have shown that immune cell subsets in disease state show different metabolic pathways to promote cell survival, lineage generation and function.

Enhanced glycolysis enables immune cells to produce sufficient ATP and biosynthetic intermediates to perform their specific effector functions [ 89 ].

In acute lymphoblastic leukemia, carcinogenic signaling induces metabolic stress, increases glucose uptake and aerobic glycolysis of activated T cells [ 91 ]. After COVID infection, monocytes and macrophages trigger mitochondrial ROS production, stabilize HIF1α expression, and promote glycolysis to maintain high viral replication level [ 92 ].

T cells in rheumatoid arthritis divert intracellular glucose to PPP and produce NADPH, which uses lactic acid from the external environment to meet their energy needs [ 93 ].

In normal kidney, the level of OXPHOS of Tregs and DCs was higher than that of glycolysis, and the two metabolic patterns were exchanged during acute kidney injury [ 94 ]. In addition, the accumulation of lactic acid in tumor promotes DCs OXPHOS and induces Tregs response [ 95 ].

Therefore, glycolysis enhancement is considered to be a marker metabolic change for the rapid activation of most immune cells. It has therapeutic potential to change the state or function of immune cells by regulating immune cell metabolism in diseases. For example, In multiple sclerosis, targeted glycolysis enhances the inhibitory ability of Tregs and affects the differentiation of proinflammatory cells [ 96 ].

Glycolysis and TCA cycle have significant changes in autoimmune diseases such as systemic lupus erythematosus. And there have been studies in animal models and preliminary human trials confirmed the efficacy of intervention in metabolic pathways. Besides, studies have shown that targeting key processes to reduce gluconeogenesis or increase glucose excretion can improve the prognosis of patients with type 1 diabetes [ 97 ].

In this review, we discuss the metabolic patterns of immune cells in different states. With the development of metabolomics, research in this field advances rapidly. However, due to the dynamic changes of the body and the complex and diverse metabolic pathways, there are still many problems to be solved in the treatment of diseases by reprogramming immune cell metabolism.

Further elucidating the mechanism of metabolism mediated by immune cells, especially in the state of disease, is expected to realize the prospect of immunotherapy in this field. Pinti M, Appay V, Campisi J, Frasca D, Fülöp T, Sauce D, Larbi A, Weinberger B, Cossarizza A Aging of the immune system: focus on inflammation and vaccination.

Eur J Immunol — Article CAS PubMed PubMed Central Google Scholar. Buck MD, Sowell RT, Kaech SM, Pearce EL Metabolic instruction of immunity. Cell — J Exp Med — Pearce EL, Pearce EJ Metabolic pathways in immune cell activation and quiescence.

Immunity — Loftus RM, Finlay DK Immunometabolism: cellular metabolism turns immune regulator. J Biol Chem — Article CAS PubMed Google Scholar. Chou WC, Rampanelli E, Li X, Ting JP Impact of intracellular innate immune receptors on immunometabolism.

Cell Mol Immunol. Article PubMed PubMed Central Google Scholar. Pearce EJ, Pearce EL Immunometabolism in driving immunity: all roads lead to metabolism. Nat Rev Immunol — Man K, Kutyavin VI, Chawla A Tissue immunometabolism: development, physiology, and pathobiology.

Cell Metab — Ferreira AV, Domiguez-Andres J, Netea MG The role of cell metabolism in innate immune memory. J Innate Immun — Muri J, Kopf M Redox regulation of immunometabolism.

Worbs T, Hammerschmidt SI, Forster R Dendritic cell migration in health and disease. Vyas JM The dendritic cell: the general of the army. Virulence — Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, Cross JR, Jung E, Thompson CB, Jones RG, Pearce EJ Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation.

Blood — Giovanelli P, Sandoval TA, Cubillos-Ruiz JR Dendritic cell metabolism and function in tumors. Trends Immunol — Pearce EJ, Everts B Dendritic cell metabolism. Wculek SK, Khouili SC, Priego E, Heras-Murillo I, Sancho D Metabolic control of dendritic cell functions: digesting information.

Front Immunol Liu J, Zhang X, Chen K, Cheng Y, Liu S, Xia M, Chen Y, Zhu H, Li Z, Cao X CCR7 chemokine receptor-inducible lnc-Dpf3 restrains dendritic cell migration by inhibiting HIF-1alpha-mediated glycolysis.

Immunity 50 — :e Article CAS Google Scholar. Guak H, Al Habyan S, Ma EH, Aldossary H, Al-Masri M, Won SY, Ying T, Fixman ED, Jones RG, McCaffrey LM, Krawczyk CM Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration.

Nat Commun de Lima TL, Peron G, Oliveira J, da Rosa LC, Thome R, Verinaud L The impact of metabolic reprogramming on dendritic cell function. Int Immunopharmacol — He Z, Zhu X, Shi Z, Wu T, Wu L Metabolic regulation of dendritic cell differentiation.

Front Immunol. Lawless SJ, Kedia-Mehta N, Walls JF, McGarrigle R, Convery O, Sinclair LV, Navarro MN, Murray J, Finlay DK Glucose represses dendritic cell-induced T cell responses.

Garg AD, Coulie PG, Van den Eynde BJ, Agostinis P Integrating next-generation dendritic cell vaccines into the current cancer immunotherapy landscape. Lee JH, Choi SY, Jung NC, Song JY, Seo HG, Lee HS, Lim DS The effect of the tumor microenvironment and tumor-derived metabolites on dendritic cell function.

J Cancer — Wynn TA, Chawla A, Pollard JW Macrophage biology in development, homeostasis and disease. Nature — Rodríguez-Prados J-C, Través PG, Cuenca J, Rico D, Aragonés J, Martín-Sanz P, Cascante M, Boscá L Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation.

J Immunol — Annu Rev Immunol — Caputa G, Flachsmann LJ, Cameron AM Macrophage metabolism: a wound-healing perspective. Immunol Cell Biol — Icard P, Fournel L, Wu Z, Alifano M, Lincet H Interconnection between metabolism and cell cycle in cancer. Trends Biochem Sci — Wang F, Zhang S, Vuckovic I, Jeon R, Lerman A, Folmes CD, Dzeja PP, Herrmann J Glycolytic stimulation is not a requirement for M2 macrophage differentiation.

Cell Metab 28 — :e4. Xie M, Yu Y, Kang R, Zhu S, Yang L, Zeng L, Sun X, Yang M, Billiar TR, Wang H, Cao L, Jiang J, Tang D PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation.

Jiang H, Shi H, Sun M, Wang Y, Meng Q, Guo P, Cao Y, Chen J, Gao X, Li E, Liu J PFKFB3-driven macrophage glycolytic metabolism is a crucial component of innate antiviral defense. Ma J, Wei K, Liu J, Tang K, Zhang H, Zhu L, Chen J, Li F, Xu P, Chen J, Liu J, Fang H, Tang L, Wang D, Zeng L, Sun W, Xie J, Liu Y, Huang B Glycogen metabolism regulates macrophage-mediated acute inflammatory responses.

Nelson VL, Nguyen HCB, Garcia-Canaveras JC, Briggs ER, Ho WY, DiSpirito JR, Marinis JM, Hill DA, Lazar MA PPARgamma is a nexus controlling alternative activation of macrophages via glutamine metabolism.

Genes Dev — Di Gioia M, Spreafico R, Springstead JR, Mendelson MM, Joehanes R, Levy D, Zanoni I Endogenous oxidized phospholipids reprogram cellular metabolism and boost hyperinflammation. Nat Immunol — Liang S, Ji L, Kang L, Hu X Metabolic regulation of innate immunity.

Adv Immunol — Van den Bossche J, Baardman J, Otto NA, van der Velden S, Neele AE, van den Berg SM, Luque-Martin R, Chen HJ, Boshuizen MC, Ahmed M, Hoeksema MA, de Vos AF, de Winther MP Mitochondrial dysfunction prevents repolarization of inflammatory macrophages.

Cell Rep — Moretta L, Bottino C, Pende D, Mingari MC, Biassoni R, Moretta A Human natural killer cells: their origin, receptors and function.

Keppel MP, Saucier N, Mah AY, Vogel TP, Cooper MA Activation-specific metabolic requirements for NK Cell IFN-gamma production. Donnelly RP, Loftus RM, Keating SE, Liou KT, Biron CA, Gardiner CM, Finlay DK mTORC1-dependent metabolic reprogramming is a prerequisite for NK cell effector function.

Mah AY, Rashidi A, Keppel MP, Saucier N, Moore EK, Alinger JB, Tripathy SK, Agarwal SK, Jeng EK, Wong HC, Miller JS, Fehniger TA, Mace EM, French AR, Cooper MA Glycolytic requirement for NK cell cytotoxicity and cytomegalovirus control. JCI Insight. Cong J, Wang X, Zheng X, Wang D, Fu B, Sun R, Tian Z, Wei H Dysfunction of natural killer cells by FBP1-induced inhibition of glycolysis during lung cancer progression.

Cell Metab 28 — :e5. Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, Kastenberger M, Bogdan C, Schleicher U, Mackensen A, Ullrich E, Fichtner-Feigl S, Kesselring R, Mack M, Ritter U, Schmid M, Blank C, Dettmer K, Oefner PJ, Hoffmann P, Walenta S, Geissler EK, Pouyssegur J, Villunger A, Steven A, Seliger B, Schreml S, Haferkamp S, Kohl E, Karrer S, Berneburg M, Herr W, Mueller-Klieser W, Renner K, Kreutz M LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells.

Souza-Fonseca-Guimaraes F, Cursons J, Huntington ND The Emergence of Natural Killer Cells as a Major Target in Cancer Immunotherapy.

Sharabi A, Tsokos GC T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy. Nat Rev Rheumatol — Masopust D, Schenkel JM The integration of T cell migration, differentiation and function.

Almeida L, Lochner M, Berod L, Sparwasser T Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol — Chapman NM, Boothby MR, Chi H Metabolic coordination of T cell quiescence and activation.

Cekic C, Sag D, Day YJ, Linden J Extracellular adenosine regulates naive T cell development and peripheral maintenance. Mueller SN, Mackay LK Tissue-resident memory T cells: local specialists in immune defence.

Moreno Ayala MA, Li Z, DuPage M Treg programming and therapeutic reprogramming in cancer. Immunology — FASEB J — J Clin Invest — Article PubMed Google Scholar. Weinberg SE, Singer BD, Steinert EM, Martinez CA, Mehta MM, Martinez-Reyes I, Gao P, Helmin KA, Abdala-Valencia H, Sena LA, Schumacker PT, Turka LA, Chandel NS Mitochondrial complex III is essential for suppressive function of regulatory T cells.

Zeng H, Yang K, Cloer C, Neale G, Vogel P, Chi H mTORC1 couples immune signals and metabolic programming to establish T reg -cell function. Cluxton D, Petrasca A, Moran B, Fletcher JM Differential regulation of human Treg and Th17 cells by fatty acid synthesis and glycolysis.

Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP, Rathmell JC The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function.

Kishton RJ, Sukumar M, Restifo NP Metabolic regulation of T cell longevity and function in tumor immunotherapy. Geltink RIK, Kyle RL, Pearce EL Unraveling the complex interplay between T cell metabolism and function.

Gitlin AD, von Boehmer L, Gazumyan A, Shulman Z, Oliveira TY, Nussenzweig MC Independent roles of switching and hypermutation in the development and persistence of B lymphocyte memory. Victora GD, Schwickert TA, Fooksman DR, Kamphorst AO, Meyer-Hermann M, Dustin ML, Nussenzweig MC Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter.

Jellusova J, Cato MH, Apgar JR, Ramezani-Rad P, Leung CR, Chen C, Richardson AD, Conner EM, Benschop RJ, Woodgett JR, Rickert RC Gsk3 is a metabolic checkpoint regulator in B cells.

Metaboilc you for Dark chocolate delicacies nature. You are using a browser Mettabolic with limited support for CSS. To obtain the best Suppotr, we recommend you use zupport more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Metabolism is a core process underlying essentially all biological functions. The integration of metabolism with immunity, known as immunometabolism, is at the forefront of immunology research, as it continues to transform the field.