Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8


Journal

Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562

Informations de publication

Date de publication:
29 Oct 2024
Historique:
received: 28 02 2024
accepted: 08 10 2024
revised: 04 10 2024
medline: 30 10 2024
pubmed: 30 10 2024
entrez: 30 10 2024
Statut: aheadofprint

Résumé

Systemic levels of methylmalonic acid (MMA), a byproduct of propionate metabolism, increase with age and MMA promotes tumor progression via its direct effects in tumor cells. However, the role of MMA in modulating the tumor ecosystem remains to be investigated. The proliferation and function of CD8

Identifiants

pubmed: 39472497
doi: 10.1038/s41388-024-03191-1
pii: 10.1038/s41388-024-03191-1
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R00CA218686
Organisme : NCI NIH HHS
ID : T32 CA233399
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : P30CA006516
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : P30CA076292
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : P01CA250984

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Cox EV, White AM. Methylmalonic acid excretion: an index of vitamin-B12 deficiency. Lancet. 1962;2:853–6.
pubmed: 14023552 doi: 10.1016/S0140-6736(62)90631-1
Rajan S, Wallace JI, Beresford SA, Brodkin KI, Allen RA, Stabler SP. Screening for cobalamin deficiency in geriatric outpatients: prevalence and influence of synthetic cobalamin intake. J Am Geriatr Soc. 2002;50:624–30.
pubmed: 11982661 doi: 10.1046/j.1532-5415.2002.50155.x
Morris MS, Jacques PF, Rosenberg IH, Selhub J. Elevated serum methylmalonic acid concentrations are common among elderly Americans. J Nutr. 2002;132:2799–803.
pubmed: 12221248 doi: 10.1093/jn/132.9.2799
Ganji V, Kafai MR. Population reference values for serum methylmalonic acid concentrations and its relationship with age, sex, race-ethnicity, supplement use, kidney function and serum vitamin B12 in the post-folic acid fortification period. Nutrients. 2018;10:74.
pubmed: 29329201 pmcid: 5793302 doi: 10.3390/nu10010074
Wang S, Liu Y, Liu J, Tian W, Zhang X, Cai H, et al. Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress, predicts all-cause and cardiovascular mortality in the general population. Redox Biol. 2020;37:101741.
pubmed: 33035815 pmcid: 7554255 doi: 10.1016/j.redox.2020.101741
Gomes AP, Ilter D, Low V, Endress JE, Fernandez-Garcia J, Rosenzweig A, et al. Age-induced accumulation of methylmalonic acid promotes tumour progression. Nature. 2020;585:283–7.
pubmed: 32814897 pmcid: 7785256 doi: 10.1038/s41586-020-2630-0
Estapé T. Cancer in the elderly: challenges and barriers. Asia Pac J Oncol Nurs. 2018;5:40–42.
pubmed: 29379832 pmcid: 5763438 doi: 10.4103/apjon.apjon_52_17
Gloeckler Ries LA, Reichman ME, Lewis DR, Hankey BF, Edwards BK. Cancer survival and incidence from the Surveillance, Epidemiology, and End Results (SEER) program. Oncologist. 2003;8:541–52.
pubmed: 14657533 doi: 10.1634/theoncologist.8-6-541
Gomes AP, Ilter D, Low V, Drapela S, Schild T, Mullarky E, et al. Altered propionate metabolism contributes to tumour progression and aggressiveness. Nat Metab. 2022;4:435–43.
pubmed: 35361954 pmcid: 9050834 doi: 10.1038/s42255-022-00553-5
Li Z, Low V, Luga V, Sun J, Earlie E, Parang B, et al. Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression. Nat Commun. 2022;13:6239.
pubmed: 36266345 pmcid: 9584945 doi: 10.1038/s41467-022-33862-0
Raskov H, Orhan A, Christensen JP, Gögenur I. Cytotoxic CD8(+) T cells in cancer and cancer immunotherapy. Br J Cancer. 2021;124:359–67.
pubmed: 32929195 doi: 10.1038/s41416-020-01048-4
Kaech SM, Cui W. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol. 2012;12:749–61.
pubmed: 23080391 pmcid: 4137483 doi: 10.1038/nri3307
McLane LM, Abdel-Hakeem MS, Wherry EJ. CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. Annu Rev Immunol. 2019;37:457–95.
pubmed: 30676822 doi: 10.1146/annurev-immunol-041015-055318
Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492–9.
pubmed: 21739672 doi: 10.1038/ni.2035
Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, et al. Defining ‘T cell exhaustion. Nat Rev Immunol. 2019;19:665–74.
pubmed: 31570879 pmcid: 7286441 doi: 10.1038/s41577-019-0221-9
Han S, Georgiev P, Ringel AE, Sharpe AH, Haigis MC. Age-associated remodeling of T cell immunity and metabolism. Cell Metab. 2023;35:36–55.
pubmed: 36473467 doi: 10.1016/j.cmet.2022.11.005
Lee KA, Shin KS, Kim GY, Song YC, Bae EA, Kim IK, et al. Characterization of age-associated exhausted CD8(+) T cells defined by increased expression of Tim-3 and PD-1. Aging Cell. 2016;15:291–300.
pubmed: 26750587 pmcid: 4783346 doi: 10.1111/acel.12435
Thommen DS, Schumacher TN. T Cell Dysfunction in Cancer. Cancer Cell. 2018;33:547–62.
pubmed: 29634943 pmcid: 7116508 doi: 10.1016/j.ccell.2018.03.012
Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15:486–99.
pubmed: 26205583 pmcid: 4889009 doi: 10.1038/nri3862
Wieland E, Shipkova M. Lymphocyte surface molecules as immune activation biomarkers. Clin Biochem. 2016;49:347–54.
pubmed: 26247177 doi: 10.1016/j.clinbiochem.2015.07.099
Ribeiro LR, Della-Pace ID, de Oliveira Ferreira AP, Funck VR, Pinton S, Bobinski F, et al. Chronic administration of methylmalonate on young rats alters neuroinflammatory markers and spatial memory. Immunobiology. 2013;218:1175–83.
pubmed: 23726524 doi: 10.1016/j.imbio.2013.04.008
Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022;50:W216–w221.
pubmed: 35325185 pmcid: 9252805 doi: 10.1093/nar/gkac194
Williams MA, Bevan MJ. Effector and memory CTL differentiation. Annu Rev Immunol. 2007;25:171–92.
pubmed: 17129182 doi: 10.1146/annurev.immunol.25.022106.141548
Bensussen A, Santana MA, Rodríguez-Jorge O. Metabolic alterations impair differentiation and effector functions of CD8+ T cells. Front Immunol. 2022;13:945980.
pubmed: 35983057 pmcid: 9380903 doi: 10.3389/fimmu.2022.945980
Møller SH, Hsueh PC, Yu YR, Zhang L, Ho PC. Metabolic programs tailor T cell immunity in viral infection, cancer, and aging. Cell Metab. 2022;34:378–95.
pubmed: 35235773 doi: 10.1016/j.cmet.2022.02.003
Tejero J, Lazure F, Gomes AP. Methylmalonic acid in aging and disease. Trends Endocrinol Metab. 2024;35:188–200.
pubmed: 38030482 doi: 10.1016/j.tem.2023.11.001
Wongkittichote P, Cunningham G, Summar ML, Pumbo E, Forny P, Baumgartner MR, et al. Tricarboxylic acid cycle enzyme activities in a mouse model of methylmalonic aciduria. Mol Genet Metab. 2019;128:444–51.
pubmed: 31648943 pmcid: 6903684 doi: 10.1016/j.ymgme.2019.10.007
Dutra JC, Dutra-Filho CS, Cardozo SE, Wannmacher CM, Sarkis JJ, Wajner M. Inhibition of succinate dehydrogenase and beta-hydroxybutyrate dehydrogenase activities by methylmalonate in brain and liver of developing rats. J Inherit Metab Dis. 1993;16:147–53.
pubmed: 8487494 doi: 10.1007/BF00711328
Brusque AM, Borba Rosa R, Schuck PF, Dalcin KB, Ribeiro CA, Silva CG, et al. Inhibition of the mitochondrial respiratory chain complex activities in rat cerebral cortex by methylmalonic acid. Neurochem Int. 2002;40:593–601.
pubmed: 11900854 doi: 10.1016/S0197-0186(01)00130-9
Jenkins E, Whitehead T, Fellermeyer M, Davis SJ, Sharma S. The current state and future of T-cell exhaustion research. Oxf Open Immunol. 2023;4:iqad006.
pubmed: 37554723 pmcid: 10352049 doi: 10.1093/oxfimm/iqad006
Khan O, Giles JR, McDonald S, Manne S, Ngiow SF, Patel KP, et al. TOX transcriptionally and epigenetically programs CD8(+) T cell exhaustion. Nature. 2019;571:211–8.
pubmed: 31207603 pmcid: 6713202 doi: 10.1038/s41586-019-1325-x
Scott AC, Dündar F, Zumbo P, Chandran SS, Klebanoff CA, Shakiba M, et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature. 2019;571:270–4.
pubmed: 31207604 pmcid: 7698992 doi: 10.1038/s41586-019-1324-y
Alfei F, Kanev K, Hofmann M, Wu M, Ghoneim HE, Roelli P, et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature. 2019;571:265–9.
pubmed: 31207605 doi: 10.1038/s41586-019-1326-9
Miller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, et al. Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade. Nat Immunol. 2019;20:326–36.
pubmed: 30778252 pmcid: 6673650 doi: 10.1038/s41590-019-0312-6
Jiang W, He Y, He W, Wu G, Zhou X, Sheng Q, et al. Exhausted CD8+T cells in the tumor immune microenvironment: new pathways to therapy. Front Immunol. 2020;11:622509.
pubmed: 33633741 doi: 10.3389/fimmu.2020.622509
Wu T, Ji Y, Moseman EA, Xu HC, Manglani M, Kirby M, et al. The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Sci Immunol. 2016;1:eaai8593.
pubmed: 28018990 pmcid: 5179228 doi: 10.1126/sciimmunol.aai8593
Gupta PK, Godec J, Wolski D, Adland E, Yates K, Pauken KE, et al. CD39 Expression Identifies Terminally Exhausted CD8+ T Cells. PLoS Pathog. 2015;11:e1005177.
pubmed: 26485519 pmcid: 4618999 doi: 10.1371/journal.ppat.1005177
Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun. 2020;11:102.
pubmed: 31900386 pmcid: 6941980 doi: 10.1038/s41467-019-13668-3
Letouzé E, Martinelli C, Loriot C, Burnichon N, Abermil N, Ottolenghi C, et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell. 2013;23:739–52.
pubmed: 23707781 doi: 10.1016/j.ccr.2013.04.018
Molina JR, Sun Y, Protopopova M, Gera S, Bandi M, Bristow C, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med. 2018;24:1036–46.
pubmed: 29892070 doi: 10.1038/s41591-018-0052-4
Sun F, Huo X, Zhai Y, Wang A, Xu J, Su D, et al. Crystal structure of mitochondrial respiratory membrane protein complex II. Cell. 2005;121:1043–57.
pubmed: 15989954 doi: 10.1016/j.cell.2005.05.025
Jackson EL, Olive KP, Tuveson DA, Bronson R, Crowley D, Brown M, et al. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res. 2005;65:10280–8.
pubmed: 16288016 doi: 10.1158/0008-5472.CAN-05-2193
Kelly JM, Sterry SJ, Cose S, Turner SJ, Fecondo J, Rodda S, et al. Identification of conserved T cell receptor CDR3 residues contacting known exposed peptide side chains from a major histocompatibility complex class I-bound determinant. Eur J Immunol. 1993;23:3318–26.
pubmed: 8258346 doi: 10.1002/eji.1830231239
Podetz-Pedersen KM, Vezys V, Somia NV, Russell SJ, McIvor RS. Cellular immune response against firefly luciferase after sleeping beauty-mediated gene transfer in vivo. Hum Gene Ther. 2014;25:955–65.
pubmed: 25093708 pmcid: 4251089 doi: 10.1089/hum.2014.048
Hu C, Ye M, Bai J, Liu P, Lu F, Chen J, et al. Methylmalonic acid promotes colorectal cancer progression via activation of Wnt/β-catenin pathway mediated epithelial-mesenchymal transition. Cancer Cell Int. 2023;23:131.
pubmed: 37403090 pmcid: 10320877 doi: 10.1186/s12935-023-02973-z
Vardhana SA, Hwee MA, Berisa M, Wells DK, Yost KE, King B, et al. Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen. Nat Immunol. 2020;21:1022–33.
pubmed: 32661364 pmcid: 7442749 doi: 10.1038/s41590-020-0725-2
Scharping NE, Rivadeneira DB, Menk AV, Vignali PDA, Ford BR, Rittenhouse NL, et al. Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion. Nat Immunol. 2021;22:205–15.
pubmed: 33398183 pmcid: 7971090 doi: 10.1038/s41590-020-00834-9
Paley MA, Kroy DC, Odorizzi PM, Johnnidis JB, Dolfi DV, Barnett BE, et al. Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection. Science. 2012;338:1220–5.
pubmed: 23197535 pmcid: 3653769 doi: 10.1126/science.1229620
Utzschneider DT, Gabriel SS, Chisanga D, Gloury R, Gubser PM, Vasanthakumar A, et al. Early precursor T cells establish and propagate T cell exhaustion in chronic infection. Nat Immunol. 2020;21:1256–66.
pubmed: 32839610 doi: 10.1038/s41590-020-0760-z
Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. 2003;77:4911–27.
pubmed: 12663797 pmcid: 152117 doi: 10.1128/JVI.77.8.4911-4927.2003
Mohamed E, Sierra RA, Trillo-Tinoco J, Cao Y, Innamarato P, Payne KK, et al. The unfolded protein response mediator PERK governs myeloid cell-driven immunosuppression in tumors through inhibition of STING signaling. Immunity. 2020;52:668–82.e667.
pubmed: 32294407 pmcid: 7207019 doi: 10.1016/j.immuni.2020.03.004

Auteurs

Joanne D Tejero (JD)

Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, 33612, USA.

Rebecca S Hesterberg (RS)

Department of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Stanislav Drapela (S)

Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Didem Ilter (D)

Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Devesh Raizada (D)

Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Felicia Lazure (F)

Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Hossein Kashfi (H)

Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Min Liu (M)

Proteomics and Metabolomics Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Leonardo Silvane (L)

Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Dorina Avram (D)

Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Juan Fernández-García (J)

Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Herestraat 49, 3000, Leuven, Belgium.
Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Herestraat 49, 3000, Leuven, Belgium.

John M Asara (JM)

Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.

Sarah-Maria Fendt (SM)

Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Herestraat 49, 3000, Leuven, Belgium.
Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Herestraat 49, 3000, Leuven, Belgium.

John L Cleveland (JL)

Department of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.

Ana P Gomes (AP)

Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA. ana.dasilvagomes@moffitt.org.

Classifications MeSH