Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function

Journal of Clinical Investigation

Volumn 123, Issue 10, 2013, Pages 4479-4488

  Sukumar, Madhusudhanan ^a   Liu, Jie ^b   Ji, Yun ^a   Subramanian, Murugan ^c   Crompton, Joseph G ^a   Yu, Zhiya ^a   Roychoudhuri, Rahul ^a   Palmer, Douglas C ^a   Muranski, Pawel ^a   Karoly, Edward D ^d   Mohney, Robert P ^d   Klebanoff, Christopher A ^a   Lal, Ashish ^c   Finkel, Toren ^b   Restifo, Nicholas P ^a   Gattinoni, Luca ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

^d METABOLON INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEOXYGLUCOSE; GLUCOSE; PHOSPHOGLYCERATE MUTASE; CANCER VACCINE; FORKHEAD TRANSCRIPTION FACTOR; FOXO1 PROTEIN, MOUSE; HEXOKINASE;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; ENZYME INHIBITION; GLUCOSE TRANSPORT; GLYCOLYSIS; LONG TERM MEMORY; LYMPHOCYTE DIFFERENTIATION; MEMORY T LYMPHOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE ACTIVATION; ACTIVE IMMUNIZATION; ADOPTIVE TRANSFER; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CANCER TRANSPLANTATION; CELL MOTION; CELL SURVIVAL; DRUG EFFECTS; ENERGY METABOLISM; ENZYMOLOGY; HUMAN; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; MELANOMA, EXPERIMENTAL; METABOLISM; PHYSIOLOGICAL STRESS; T LYMPHOCYTE; TUMOR CELL LINE; TUMOR VOLUME;

ADOPTIVE TRANSFER; ANIMALS; CANCER VACCINES; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE, TUMOR; CELL MOVEMENT; CELL SURVIVAL; DEOXYGLUCOSE; ENERGY METABOLISM; FORKHEAD TRANSCRIPTION FACTORS; GLYCOLYSIS; HEXOKINASE; HUMANS; IMMUNOLOGIC MEMORY; IMMUNOTHERAPY, ACTIVE; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED C57BL; NEOPLASM TRANSPLANTATION; STRESS, PHYSIOLOGICAL; T-LYMPHOCYTES; TUMOR BURDEN;

EID: 84885055994     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI69589     Document Type: Article

References (55)

1. Williams MA, Bevan MJ. Effector and memory CTL differentiation. Annu Rev Immunol. 2007;25:171-192.
2. Klebanoff CA, Gattinoni L, Restifo NP. CD8+ T-cell memory in tumor immunology and immunotherapy. Immunol Rev. 2006;211:214-224.
3. Gattinoni L, Klebanoff CA, Restifo NP. Paths to stemness: building the ultimate antitumour T cell. Nat Rev Cancer. 2012;12(10):671-684.
4. Gattinoni L, et al. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat Med. 2009;15(7):808-813.
5. Gattinoni L, et al. A human memory T cell subset with stem cell-like properties. Nat Med. 2011;17(10):1290-1297.
6. Wherry EJ, et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol. 2003;4(3):225-234.
7. Thaventhiran JE, Fearon DT, Gattinoni L. Transcriptional regulation of effector and memory CD8 T cell fates. Curr Opin Immunol. 2013;25(3):321-328.
8. Kaech SM, Cui W. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol. 2012;12(11):749-761.
9. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31:259-283.
10. Michalek RD, Rathmell JC. The metabolic life and times of a T-cell. Immunol Rev. 2010;236:190-202.
11. van der Windt GJ, Pearce EL. Metabolic switching and fuel choice during T-cell differentiation and memory development. Immunol Rev. 2012;249(1):27-42.
12. Powell JD, Pollizzi K. Fueling memories. Immunity. 2012;36(1):3-5.
13. Gerriets VA, Rathmell JC. Metabolic pathways in T cell fate and function. Trends Immunol. 2012;33(4):168-173.
14. Wang R, Green DR. Metabolic checkpoints in activated T cells. Nat Immunol. 2012;13(10):907-915.
15. Frauwirth KA, et al. The CD28 signaling pathway regulates glucose metabolism. Immunity. 2002;16(6):769-777.
16. Jones RG, Thompson CB. Revving the engine: signal transduction fuels T cell activation. Immunity. 2007;27(2):173-178.
17. Wang R, et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity. 2011;35(6):871-882.
18. Chang CH, et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell. 2013;153(6):1239-1251.
19. Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity. 2013;38(4):633-643.
20. Tejera MM, Kim EH, Sullivan JA, Plisch EH, Suresh M. FoxO1 controls effector-to-memory transition and maintenance of functional CD8 T cell memory. J Immunol. 2013;191(1):187-199.
21. Pearce EL, et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature. 2009;460(7251):103-107.
22. van der Windt GJ, et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 2011;36(1):68-78.
23. Araki K, et al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009;460(7251):108-112.
24. Yamada K, Saito M, Matsuoka H, Inagaki N. A realtime method of imaging glucose uptake in single, living mammalian cells. Nat Protoc. 2007;2(3):753-762.
25. Zhong L, et al. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell. 2010;140(2):280-293.
26. Kalia V, Sarkar S, Subramaniam S, Haining WN, Smith KA, Ahmed R. Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. Immunity. 2010;32(1):91-103.
27. Zhou X, Yu S, Zhao DM, Harty JT, Badovinac VP, Xue HH. Differentiation and persistence of memory CD8 (+) T cells depend on T cell factor 1. Immunity. 2010;33(2):229-240.
28. Jeannet G, Boudousquie C, Gardiol N, Kang J, Huelsken J, Held W. Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory. Proc Natl Acad Sci U S A. 2010;107(21):9777-9782.
29. Ichii H, et al. Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells. Nat Immunol. 2002;3(6):558-563.
30. Shin H, et al. A role for the transcriptional repressor Blimp-1 in CD8 (+) T cell exhaustion during chronic viral infection. Immunity. 2009;31(2):309-320.
31. Rutishauser RL, et al. Transcriptional repressor Blimp-1 promotes CD8 (+) T cell terminal differentiation and represses the acquisition of central memory T cell properties. Immunity. 2009;31(2):296-308.
32. Kallies A, Xin A, Belz GT, Nutt SL. Blimp-1 transcription factor is required for the differentiation of effector CD8 (+) T cells and memory responses. Immunity. 2009;31(2):283-295.
33. Ji Y, et al. Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. Nat Immunol. 2011;12(12):1230-1237.
34. Hallows WC, Yu W, Denu JM. Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1 protein-mediated deacetylation. J Biol Chem. 2012;287(6):3850-3858.
35. Kondoh H, et al. Glycolytic enzymes can modulate cellular life span. Cancer Res. 2005;65(1):177-185.
36. Cham CM, Driessens G, O'Keefe JP, Gajewski TF. Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells. Eur J Immunol. 2008;38(9):2438-2450.
37. Shi LZ, et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. 2011;208(7):1367-1376.
38. Michalek RD, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 2011;186(6):3299-3303.
39. Rolf J, Zarrouk M, Finlay DK, Foretz M, Viollet B, Cantrell DA. AMPKalpha1: A glucose sensor that controls CD8 T-cell memory. Eur J Immunol. 2013;43(4):889-896.
40. Finlay DK, et al. PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J Exp Med. 2012;209(13):2441-2453.
41. Hess MR, Doedens AL, Goldrath AW, Hedrick SM. Differentiation of CD8 memory T cells depends on Foxo1. J Exp Med. 2013;210(6):1189-1200.
42. Rao RR, Li Q, Gubbels Bupp MR, Shrikant PA. Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8 (+) T cell differentiation. Immunity. 2012;36(3):374-387.
43. Macintyre AN, et al. Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism. Immunity. 2011;34(2):224-236.
44. Kerdiles YM, et al. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat Immunol. 2009;10(2):176-184.
45. Finlay D, Cantrell DA. Metabolism, migration and memory in cytotoxic T cells. Nat Rev Immunol. 2011;11(2):109-117.
46. Gattinoni L, et al. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J Clin Invest. 2005;115(6):1616-1626.
47. Klebanoff CA, et al. Central memory self/tumorreactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci U S A. 2005;102(27):9571-9576.
48. Nolz JC, Harty JT. Protective capacity of memory CD8+ T cells is dictated by antigen exposure history and nature of the infection. Immunity. 2011;34(5):781-793.
49. Muranski P, et al. Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity. 2011;35(6):972-985.
50. Rosenberg SA, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550-4557.
51. Dudda JC, et al. MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer. Immunity. 2013;38(4):742-753.
52. Topalian SL, Muul LM, Solomon D, Rosenberg SA. Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. J Immunol Methods. 1987;102(1):127-141.
53. Riddell SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science. 1992;257(5067):238-241.
54. Gattinoni L, Klebanoff CA, Restifo NP. Pharmacologic induction of CD8+ T cell memory: better living through chemistry. Sci Transl Med. 2009;1(11):11ps12.
55. Lal A, Mazan-Mamczarz K, Kawai T, Yang X, Martindale JL, Gorospe M. Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs. EMBO J. 2004;23(15):3092-3102.