Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8+ T cells to suppress anti-tumor immunity

Cox EV, White AM. Methylmalonic acid excretion: an index of vitamin-B12 deficiency. Lancet. 1962;2:853–6.

Article  CAS  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

Morris MS, Jacques PF, Rosenberg IH, Selhub J. Elevated serum methylmalonic acid concentrations are common among elderly Americans. J Nutr. 2002;132:2799–803.

Article  CAS  PubMed  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Estapé T. Cancer in the elderly: challenges and barriers. Asia Pac J Oncol Nurs. 2018;5:40–42.

Article  PubMed  PubMed Central  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Raskov H, Orhan A, Christensen JP, Gögenur I. Cytotoxic CD8(+) T cells in cancer and cancer immunotherapy. Br J Cancer. 2021;124:359–67.

Article  CAS  PubMed  Google Scholar 

Kaech SM, Cui W. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol. 2012;12:749–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

McLane LM, Abdel-Hakeem MS, Wherry EJ. CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. Annu Rev Immunol. 2019;37:457–95.

Article  CAS  PubMed  Google Scholar 

Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492–9.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Thommen DS, Schumacher TN. T Cell Dysfunction in Cancer. Cancer Cell. 2018;33:547–62.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15:486–99.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wieland E, Shipkova M. Lymphocyte surface molecules as immune activation biomarkers. Clin Biochem. 2016;49:347–54.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Williams MA, Bevan MJ. Effector and memory CTL differentiation. Annu Rev Immunol. 2007;25:171–92.

Article  CAS  PubMed  Google Scholar 

Bensussen A, Santana MA, Rodríguez-Jorge O. Metabolic alterations impair differentiation and effector functions of CD8+ T cells. Front Immunol. 2022;13:945980.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  PubMed  Google Scholar 

Tejero J, Lazure F, Gomes AP. Methylmalonic acid in aging and disease. Trends Endocrinol Metab. 2024;35:188–200.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed 

留言 (0)

沒有登入
gif