Mechanisms of T‑cell metabolic reprogramming in the microenvironment of acute myeloid leukemia and its therapeutic potential (Review)
- Authors:
- Yanhong Luo
- Jie Luo
- Min Yang
- Xueya Zhao
-
Affiliations: Department of Hematology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China, Bishan Hospital of Chongqing Medical University, Chongqing 402760, P.R. China, Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, P.R. China - Published online on: July 22, 2025 https://doi.org/10.3892/ol.2025.15201
- Article Number: 455
-
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
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|
Döhner H, Weisdorf DJ and Bloomfield CD: Acute myeloid leukemia. N Engl J Med. 373:1136–1152. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Liu H: Emerging agents and regimens for AML. J Hematol Oncol. 14:492021. View Article : Google Scholar : PubMed/NCBI | |
|
Peng C, Xu Y, Wu J, Wu D, Zhou L and Xia X: TME-related biomimetic strategies against cancer. Int J Nanomedicine. 19:109–135. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Bawek S, Gurusinghe S, Burwinkel M and Przespolewski A: Updates in novel immunotherapeutic strategies for relapsed/refractory AML. Front Oncol. 14:13749632024. View Article : Google Scholar : PubMed/NCBI | |
|
Menter T and Tzankov A: Tumor microenvironment in acute myeloid leukemia: Adjusting niches. Front Immunol. 13:8111442022. View Article : Google Scholar : PubMed/NCBI | |
|
Lamble AJ and Lind EF: Targeting the immune microenvironment in acute myeloid leukemia: A focus on T cell immunity. Front Oncol. 8:2132018. View Article : Google Scholar : PubMed/NCBI | |
|
Korn C and Méndez-Ferrer S: Myeloid malignancies and the microenvironment. Blood. 129:811–822. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Rieger CT and Fiegl M: Microenvironmental oxygen partial pressure in acute myeloid leukemia: Is there really a role for hypoxia? Exp Hematol. 44:578–582. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Yu S and Jiang J: Immune infiltration-related genes regulate the progression of AML by invading the bone marrow microenvironment. Front Immunol. 15:14099452024. View Article : Google Scholar : PubMed/NCBI | |
|
Zeng T, Cui L, Huang W, Liu Y, Si C, Qian T, Deng C and Fu L: The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia. BMC Med. 19:1762021. View Article : Google Scholar : PubMed/NCBI | |
|
Chraa D, Naim A, Olive D and Badou A: T lymphocyte subsets in cancer immunity: Friends or foes. J Leukoc Biol. 105:243–255. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Plitas G and Rudensky AY: Regulatory T cells: Differentiation and function. Cancer Immunol Res. 4:721–725. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
MacIver NJ, Michalek RD and Rathmell JC: Metabolic regulation of T lymphocytes. Annu Rev Immunol. 31:259–283. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Lochner M, Berod L and Sparwasser T: Fatty acid metabolism in the regulation of T cell function. Trends Immunol. 36:81–91. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Endo Y, Kanno T and Nakajima T: Fatty acid metabolism in T-cell function and differentiation. Int Immunol. 34:579–587. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y, Fuhrer T, Kogadeeva M, Picotti P, Meissner F, Mann M, et al: L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell. 167:829–842.e13. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, He Y, Hu F, Hu C, Sun Y, Yang K and Yang S: Metabolic reprogramming of immune cells in the tumor microenvironment. Int J Mol Sci. 25:122232024. View Article : Google Scholar : PubMed/NCBI | |
|
Halestrap AP: The monocarboxylate transporter family-structure and functional characterization. IUBMB Life. 64:1–9. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Uhl FM, Chen S, O'Sullivan D, Edwards-Hicks J, Richter G, Haring E, Andrieux G, Halbach S, Apostolova P, Büscher J, et al: Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans. Sci Transl Med. 12:eabb89692020. View Article : Google Scholar : PubMed/NCBI | |
|
Ju HQ, Zhan G, Huang A, Sun Y, Wen S, Yang J, Lu WH, Xu RH, Li J, Li Y, et al: ITD mutation in FLT3 tyrosine kinase promotes Warburg effect and renders therapeutic sensitivity to glycolytic inhibition. Leukemia. 31:2143–2150. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Herst PM, Howman RA, Neeson PJ, Berridge MV and Ritchie DS: The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome. J Leukoc Biol. 89:51–55. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Herst PM, Hesketh EL, Ritchie DS and Berridge MV: Glycolytic metabolism confers resistance to combined all-trans retinoic acid and arsenic trioxide-induced apoptosis in HL60rho0 cells. Leuk Res. 32:327–333. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Jones RG and Thompson CB: Tumor suppressors and cell metabolism: A recipe for cancer growth. Genes Dev. 23:537–548. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Röhrig F and Schulze A: The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer. 16:732–749. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Heintzman DR, Fisher EL and Rathmell JC: Microenvironmental influences on T cell immunity in cancer and inflammation. Cell Mol Immunol. 19:316–326. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Zha C, Yang X, Yang J, Zhang Y and Huang R: Immunosuppressive microenvironment in acute myeloid leukemia: Overview, therapeutic targets and corresponding strategies. Ann Hematol. 103:4883–4899. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Böttcher M, Baur R, Stoll A, Mackensen A and Mougiakakos D: Linking immunoevasion and metabolic reprogramming in B-cell-derived lymphomas. Front Oncol. 10:5947822020. View Article : Google Scholar : PubMed/NCBI | |
|
Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, et al: Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 109:3812–3819. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Chen Y, Feng Z, Kuang X, Zhao P, Chen B, Fang Q, Cheng W and Wang J: Increased lactate in AML blasts upregulates TOX expression, leading to exhaustion of CD8+ cytolytic T cells. Am J Cancer Res. 11:5726–6742. 2021.PubMed/NCBI | |
|
Voskoboinik I, Whisstock JC and Trapani JA: Perforin and granzymes: Function, dysfunction and human pathology. Nat Rev Immunol. 15:388–400. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Sradhanjali S and Reddy MM: Inhibition of pyruvate dehydrogenase kinase as a therapeutic strategy against cancer. Curr Top Med Chem. 18:444–453. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Rostamian H, Khakpoor-Koosheh M, Jafarzadeh L, Masoumi E, Fallah-Mehrjardi K, Tavassolifar MJ, M Pawelek J, Mirzaei HR and Hadjati J: Restricting tumor lactic acid metabolism using dichloroacetate improves T cell functions. BMC Cancer. 22:392022. View Article : Google Scholar : PubMed/NCBI | |
|
Kumagai S, Koyama S, Itahashi K, Tanegashima T, Lin YT, Togashi Y, Kamada T, Irie T, Okumura G, Kono H, et al: Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer Cell. 40:201–218.e9. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Yang P, Sun Y, Zhang M, Hu L, Wang X, Luo L, Qiao C, Wang J, Xiao H, Li X, et al: The inhibition of CD4+ T cell proinflammatory response by lactic acid is independent of monocarboxylate transporter 1. Scand J Immunol. 94:e131032021. View Article : Google Scholar | |
|
Jiang F, Mao Y, Lu B, Zhou G and Wang J: A hypoxia risk signature for the tumor immune microenvironment evaluation and prognosis prediction in acute myeloid leukemia. Sci Rep. 11:146572021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu X, Wang L, Kang Q, Feng C and Wang J: A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia contributing to poor prognosis through immune microenvironment and drug resistance in acute myeloid leukemia. Front Pharmacol. 15:13394652024. View Article : Google Scholar : PubMed/NCBI | |
|
Augustin RC, Delgoffe GM and Najjar YG: Characteristics of the tumor microenvironment that influence immune cell functions: Hypoxia, oxidative stress, metabolic alterations. Cancers (Basel). 12:38022020. View Article : Google Scholar : PubMed/NCBI | |
|
Jacque N, Ronchetti AM, Larrue C, Meunier G, Birsen R, Willems L, Saland E, Decroocq J, Maciel TT, Lambert M, et al: Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood. 126:1346–1356. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Carr EL, Kelman A, Wu GS, Gopaul R, Senkevitch E, Aghvanyan A, Turay AM and Frauwirth KA: Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J Immunol. 185:1037–1044. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Klysz D, Tai XG, Robert PA, Craveiro M, Cretenet G, Oburoglu L, Mongellaz C, Floess S, Fritz V, Matias MI, et al: Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation. Sci Signal. 8:ra972015. View Article : Google Scholar : PubMed/NCBI | |
|
Sun LY, Li XJ, Sun YM, Huang W, Fang K, Han C, Chen ZH, Luo XQ, Chen YQ and Wang WT: LncRNA ANRIL regulates AML development through modulating the glucose metabolism pathway of AdipoR1/AMPK/SIRT1. Mol Cancer. 17:1272018. View Article : Google Scholar : PubMed/NCBI | |
|
Balihodzic A, Barth DA, Prinz F and Pichler M: Involvement of long non-coding RNAs in glucose metabolism in cancer. Cancers (Basel). 13:9772021. View Article : Google Scholar : PubMed/NCBI | |
|
Pavlova NN, Zhu J and Thompson CB: The hallmarks of cancer metabolism: Still emerging. Cell Metab. 34:355–377. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Cunningham I and Kohno B: 18 FDG-PET/CT: 21st century approach to leukemic tumors in 124 cases. Am J Hematol. 91:379–384. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wang R, Feng W, Wang H, Wang L, Yang X, Yang F, Zhang Y, Liu X, Zhang D, Ren Q, et al: Blocking migration of regulatory T cells to leukemic hematopoietic microenvironment delays disease progression in mouse leukemia model. Cancer Lett. 469:151–161. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Bakker E, Qattan M, Mutti L, Demonacos C and Krstic-Demonacos M: The role of microenvironment and immunity in drug response in leukemia. Biochim Biophys Acta. 1863:414–426. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang M, Yang Y, Liu J, Guo L, Guo Q and Liu W: Bone marrow immune cells and drug resistance in acute myeloid leukemia. Exp Biol Med (Maywood). 250:102352025. View Article : Google Scholar : PubMed/NCBI | |
|
Ciciarello M, Corradi G, Forte D, Cavo M and Curti A: Emerging bone marrow microenvironment-driven mechanisms of drug resistance in acute myeloid leukemia: Tangle or chance? Cancers (Basel). 13:53192021. View Article : Google Scholar : PubMed/NCBI | |
|
Feske S, Colucci F and Coetzee WA: Do KATP channels have a role in immunity? Front Immunol. 15:14849712024. View Article : Google Scholar : PubMed/NCBI | |
|
Feske S, Wulff H and Skolnik EY: Ion channels in innate and adaptive immunity. Annu Rev Immunol. 33:291–353. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Eil R, Vodnala SK, Clever D, Klebanoff CA, Sukumar M, Pan JH, Palmer DC, Gros A, Yamamoto TN, Patel SJ, et al: Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature. 537:539–543. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Vodnala SK, Eil R, Kishton RJ, Sukumar M, Yamamoto TN, Ha NH, Lee PH, Shin M, Patel SJ, Yu Z, et al: T cell stemness and dysfunction in tumors are triggered by a common mechanism. Science. 363:eaau01352019. View Article : Google Scholar : PubMed/NCBI | |
|
Almeida L, Lochner M, Berod L and Sparwasser T: Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 28:514–524. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Fukushi A, Kim HD, Chang YC and Kim CH: Revisited metabolic control and reprogramming cancers by means of the warburg effect in tumor cells. Int J Mol Sci. 23:100372022. View Article : Google Scholar : PubMed/NCBI | |
|
Riether C: Regulation of hematopoietic and leukemia stem cells by regulatory T cells. Front Immunol. 13:10493012022. View Article : Google Scholar : PubMed/NCBI | |
|
Epperly R, Gottschalk S and Velasquez MP: A bump in the road: how the hostile AML microenvironment affects CAR T cell therapy. Front Oncol. 10:2622020. View Article : Google Scholar : PubMed/NCBI | |
|
Han Y, Dong Y, Yang Q, Xu W, Jiang S, Yu Z, Yu K and Zhang S: Acute myeloid leukemia cells express ICOS ligand to promote the expansion of regulatory T cells. Front Immunol. 9:22272018. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou Q, Bucher C, Munger ME, Highfill SL, Tolar J, Munn DH, Levine BL, Riddle M, June CH, Vallera DA, et al: Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Blood. 114:3793–3802. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Liu SY, Liao S, Liang L, Deng J and Zhou Y: The relationship between CD4+ T cell glycolysis and their functions. Trends Endocrinol Metab. 34:345–360. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Cao J, Liao S, Zeng F, Liao Q, Luo G and Zhou Y: Effects of altered glycolysis levels on CD8+ T cell activation and function. Cell Death Dis. 14:4072023. View Article : Google Scholar : PubMed/NCBI | |
|
Yao CC, Sun RM, Yang Y, Zhou HY, Meng ZW, Chi R, Xia LL, Ji P, Chen YY, Zhang GQ, et al: Accumulation of branched-chain amino acids reprograms glucose metabolism in CD8+ T cells with enhanced effector function and anti-tumor response. Cell Rep. 42:1121862023. View Article : Google Scholar : PubMed/NCBI | |
|
Rabbani N and Thornalley PJ: Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome. Amino Acids. 42:1133–1142. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Palanissami G and Paul SFD: AGEs and RAGE: Metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers. Explor Target Antitumor Ther. 4:812–849. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Waghela BN, Vaidya FU, Ranjan K, Chhipa AS, Tiwari BS and Pathak C: AGE-RAGE synergy influences programmed cell death signaling to promote cancer. Mol Cell Biochem. 476:585–598. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Bakhtiyari M, Liaghat M, Aziziyan F, Shapourian H, Yahyazadeh S, Alipour M, Shahveh S, Maleki-Sheikhabadi F, Halimi H, Forghaniesfidvajani R, et al: The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: Immune checkpoints, metabolic checkpoints, and signaling pathways. Cell Commun Signal. 21:2522023. View Article : Google Scholar : PubMed/NCBI | |
|
Wang R, Liu Z, Fan Z and Zhan H: Lipid metabolism reprogramming of CD8+ T cell and therapeutic implications in cancer. Cancer Lett. 567:2162672023. View Article : Google Scholar : PubMed/NCBI | |
|
Jameson SC and Masopust D: Understanding subset diversity in T cell memory. Immunity. 48:214–226. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kaech SM and Cui W: Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol. 12:749–761. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
D'Cruz LM, Rubinstein MP and Goldrath AW: Surviving the crash: Transitioning from effector to memory CD8+ T cell. Semin Immunol. 21:92–98. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Mougiakakos D: The induction of a permissive environment to promote T cell immune evasion in acute myeloid leukemia: The metabolic perspective. Front Oncol. 9:11662019. View Article : Google Scholar : PubMed/NCBI | |
|
Noviello M, Manfredi F, Ruggiero E, Perini T, Oliveira G, Cortesi F, De Simone P, Toffalori C, Gambacorta V, Greco R, et al: Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT. Nat Commun. 10:10652019. View Article : Google Scholar : PubMed/NCBI | |
|
Abbas HA, Hao D, Tomczak K, Barrodia P, Im JS, Reville PK, Alaniz Z, Wang W, Wang R, Wang F, et al: Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy. Nat Commun. 12:60712021. View Article : Google Scholar : PubMed/NCBI | |
|
Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, Jones RG and Choi Y: Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature. 460:103–107. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Raud B, McGuire PJ, Jones RG, Sparwasser T and Berod L: Fatty acid metabolism in CD8+ T cell memory: Challenging current concepts. Immunol Rev. 283:213–231. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
van der Windt GJW, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, Pearce EJ and Pearce EL: Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 36:68–78. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, Larsen CP and Ahmed R: mTOR regulates memory CD8 T-cell differentiation. Nature. 460:108–112. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Li P, Yin YL, Li D, Woo Kim S and Wu G: Amino acids and immune function. Br J Nutr. 98:237–252. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Bai C, Ruan Y, Liu M, Chu Q, Qiu L, Yang C and Li B: Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia. Nat Commun. 10:2012019. View Article : Google Scholar : PubMed/NCBI | |
|
Leone RD, Zhao L, Englert JM, Sun IM, Oh MH, Sun IH, Arwood ML, Bettencourt IA, Patel CH, Wen J, et al: Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science. 366:1013–1021. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A and Mellor AL: Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med. 189:1363–1372. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Murray PJ: Amino acid auxotrophy as a system of immunological control nodes. Nat Immunol. 17:132–139. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Di Marcantonio D, Martinez E, Kanefsky JS, Huhn JM, Gabbasov R, Gupta A, Krais JJ, Peri S, Tan Y, Skorski T, et al: ATF3 coordinates serine and nucleotide metabolism to drive cell cycle progression in acute myeloid leukemia. Mol Cell. 81:2752–2764.e6. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Yabushita T and Goyama S: Nucleic acid metabolism: The key therapeutic target for myeloid tumors. Exp Hematol. 142:1046932025. View Article : Google Scholar : PubMed/NCBI | |
|
Capelletti MM, Montini O, Ruini E, Tettamanti S, Savino AM and Sarno J: Unlocking the heterogeneity in acute leukaemia: Dissection of clonal architecture and metabolic properties for clinical interventions. Int J Mol Sci. 26:452024. View Article : Google Scholar : PubMed/NCBI | |
|
Wu HL, Gong Y, Ji P, Xie YF, Jiang YZ and Liu GY: Targeting nucleotide metabolism: A promising approach to enhance cancer immunotherapy. J Hematol Oncol. 15:452022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H, Wei Y and Wang N: Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia. Purinergic Signal. Mar 6–2024.(Epub ahead of print). View Article : Google Scholar | |
|
Ohta A: A metabolic immune checkpoint: Adenosine in tumor microenvironment. Front Immunol. 7:1092016. View Article : Google Scholar : PubMed/NCBI | |
|
Evans DR and Guy HI: Mammalian pyrimidine biosynthesis: Fresh insights into an ancient pathway. J Biol Chem. 279:33035–33038. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Santi A, Caselli A, Paoli P, Corti D, Camici G, Pieraccini G, Taddei ML, Serni S, Chiarugi P and Cirri P: The effects of CA IX catalysis products within tumor microenvironment. Cell Commun Signal. 11:812013. View Article : Google Scholar : PubMed/NCBI | |
|
Pollizzi KN, Patel CH, Sun IH, Oh MH, Waickman AT, Wen J, Delgoffe GM and Powell JD: mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation. J Clin Invest. 125:2090–2108. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Dabi YT, Andualem H, Degechisa ST and Gizaw ST: Targeting metabolic reprogramming of T-cells for enhanced anti-tumor response. Biologics. 16:35–45. 2022.PubMed/NCBI | |
|
Saravia J, Raynor JL, Chapman NM, Lim SA and Chi H: Signaling networks in immunometabolism. Cell Res. 30:328–342. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Yan Y, Huang L, Liu Y, Yi M, Chu Q, Jiao D and Wu K: Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: Implications for antitumor immunity. J Hematol Oncol. 15:1042022. View Article : Google Scholar : PubMed/NCBI | |
|
Castro I, Sampaio-Marques B and Ludovico P: Targeting metabolic reprogramming in acute myeloid leukemia. Cells. 8:9672019. View Article : Google Scholar : PubMed/NCBI | |
|
Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M and Evans RM: PPARγ signaling and metabolism: The good, the bad and the future. Nat Med. 19:557–566. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Angela M, Endo Y, Asou HK, Yamamoto T, Tumes DJ, Tokuyama H, Yokote K and Nakayama T: Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells. Nat Commun. 7:136832016. View Article : Google Scholar : PubMed/NCBI | |
|
Tabe Y, Konopleva M and Andreeff M: Fatty acid metabolism, bone marrow adipocytes, and AML. Front Oncol. 10:1552020. View Article : Google Scholar : PubMed/NCBI | |
|
Chowdhury PS, Chamoto K, Kumar A and Honjo T: PPAR-induced fatty acid oxidation in T cells increases the number of tumor-reactive CD8+ T cells and facilitates anti-PD-1 therapy. Cancer Immunol Res. 6:1375–1387. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang JZ, Behrooz A and Ismail-Beigi F: Regulation of glucose transport by hypoxia. Am J Kidney Dis. 34:189–202. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Miska J, Lee-Chang C, Rashidi A, Muroski ME, Chang AL, Lopez-Rosas A, Zhang P, Panek WK, Cordero A, Han Y, et al: HIF-1α is a metabolic switch between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression of tregs in glioblastoma. Cell Rep. 27:226–237.e4. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Nagao A, Kobayashi M, Koyasu S, Chow CCT and Harada H: HIF-1-dependent reprogramming of glucose metabolic pathway of cancer cells and its therapeutic significance. Int J Mol Sci. 20:2382019. View Article : Google Scholar : PubMed/NCBI | |
|
Wu H, Zhao X, Hochrein SM, Eckstein M, Gubert GF, Knöpper K, Mansilla AM, Öner A, Doucet-Ladevèze R, Schmitz W, et al: Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming. Nat Commun. 14:68582023. View Article : Google Scholar : PubMed/NCBI | |
|
Pan F, Barbi J and Pardoll DM: Hypoxia-inducible factor 1: A link between metabolism and T cell differentiation and a potential therapeutic target. Oncoimmunology. 1:510–515. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Alatrash G, Daver N and Mittendorf EA: Targeting immune checkpoints in hematologic malignancies. Pharmacol Rev. 68:1014–1025. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Stahl M and Goldberg AD: Immune checkpoint inhibitors in acute myeloid leukemia: Novel combinations and therapeutic targets. Curr Oncol Rep. 21:372019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou Q, Munger ME, Highfill SL, Tolar J, Weigel BJ, Riddle M, Sharpe AH, Vallera DA, Azuma M, Levine BL, et al: Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood. 116:2484–2493. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Sadelain M, Brentjens R and Rivière I: The basic principles of chimeric antigen receptor design. Cancer Discov. 3:388–398. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Riddell SR, Jensen MC and June CH: Chimeric antigen receptor-modified T cells: Clinical translation in stem cell transplantation and beyond. Biol Blood Marrow Transplant. 19 (1 Suppl):S2–S5. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Suryadevara CM, Desai R, Farber SH, Choi BD, Swartz AM, Shen SH, Gedeon PC, Snyder DJ, Herndon JE II, Healy P, et al: Preventing Lck activation in CAR T cells confers treg resistance but requires 4-1BB signaling for them to persist and treat solid tumors in nonlymphodepleted hosts. Clin Cancer Res. 25:358–368. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Mussai F, Wheat R, Sarrou E, Booth S, Stavrou V, Fultang L, Perry T, Kearns P, Cheng P, Keeshan K, et al: Targeting the arginine metabolic brake enhances immunotherapy for leukaemia. Int J Cancer. 145:2201–2208. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Beavis PA, Henderson MA, Giuffrida L, Mills JK, Sek K, Cross RS, Davenport AJ, John LB, Mardiana S, Slaney CY, et al: Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy. J Clin Invest. 127:929–941. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Leone RD, Sun IM, Oh MH, Sun IH, Wen J, Englert J and Powell JD: Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models. Cancer Immunol Immunother. 67:1271–1284. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Mussai F, De Santo C, Abu-Dayyeh I, Booth S, Quek L, McEwen-Smith RM, Qureshi A, Dazzi F, Vyas P and Cerundolo V: Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood. 122:749–758. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, Karoly ED, Freeman GJ, Petkova V, Seth P, et al: PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun. 6:66922015. View Article : Google Scholar : PubMed/NCBI |
