Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance

Clinical and Experimental Immunology

Volumn 161, Issue 2, 2010, Pages 298-305

  Lee, S Y ^a,a   Lee, K J ^a   Moon, J Y ^a   Choi, H K ^a   Kim, H O ^a   Hur, G Y ^a   Jung, K H ^a   Kim, J H ^a   Shin, C ^a   Shim, J J ^a   In, K H ^a   Yoo, S H ^a   Kang, K H ^a  

^a Korea University College of Medicine   (South Korea)

Author keywords

indoleamine 2,3 dioxygenase; interleukin 10; regulatory T cell; statin; transforming growth factor

Indexed keywords

BETA ACTIN; CYCLIN D1; INDOLEAMINE 2,3 DIOXYGENASE; INTERLEUKIN 10; SIMVASTATIN; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER CELL CULTURE; CANCER MODEL; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG EFFECT; DRUG MEGADOSE; DRUG POTENCY; GROWTH RATE; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; LOW DRUG DOSE; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; TUMOR IMMUNITY;

ANIMALS; CELL COUNT; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN D1; CYTOSTATIC AGENTS; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION; HUMANS; IMMUNE TOLERANCE; IMMUNOSUPPRESSIVE AGENTS; INDOLEAMINE-PYRROLE 2,3,-DIOXYGENASE; INTERLEUKIN-10; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; MICE; MICE, INBRED C57BL; NEOPLASMS; SIMVASTATIN; SPLEEN; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA;

EID: 77954639908     PISSN: 00099104     EISSN: 13652249     Source Type: Journal    
DOI: 10.1111/j.1365-2249.2010.04170.x     Document Type: Article

References (34)

1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994 344 : 1383 9.
2. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998 339 : 1349 57.
3. Graaf MR, Richel DJ, van Noorden CJ, Guchelaar HJ. Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer. Cancer Treat Rev 2004 30 : 609 41.
4. Jakobisiak M, Golab J. Potential antitumor effects of statins Review Int J Oncol 2003 23 : 1055 69.
5. Keyomarsi K, Sandoval L, Band V, Pardee AB. Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res 1991 51 : 3602 9.
6. Xia Z, Tan MM, Wong WW, Dimitroulakos J, Minden MD, Penn LZ. Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells. Leukemia 2001 15 : 1398 407.
7. Kusama T, Mukai M, Iwasaki T et al. Inhibition of epidermal growth factor-induced RhoA translocation and invasion of human pancreatic cancer cells by 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors. Cancer Res 2001 61 : 4885 91.
8. Miller AC, Kariko K, Myers CE, Clark EP, Samid D. Increased radioresistance of EJras-transformed human osteosarcoma cells and its modulation by lovastatin, an inhibitor of p21ras isoprenylation. Int J Cancer 1993 53 : 302 7.
9. Youssef S, Stuve O, Patarroyo JC et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002 420 : 78 84.
10. Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet 1999 353 : 983 4.
11. Mausner-Fainberg K, Luboshits G, Mor A et al. The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells. Atherosclerosis 2008 197 : 829 39.
12. Mira E, Leon B, Barber DF et al. Statins induce regulatory T cell recruitment via a CCL1 dependent pathway. J Immunol 2008 181 : 3524 34.
13. Cordle A, Koenigsknecht-Talboo J, Wilkinson B, Limpert A, Landreth G. Mechanisms of statin-mediated inhibition of small G-protein function. J Biol Chem 2005 280 : 34202 9.
14. Blanco-Colio LM, Tunon J, Martin-Ventura JL, Egido J. Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 2003 63 : 12 23.
15. Goldstein MR, Mascitelli L, Pezzetta F. Statins, Tregs and cancer. Atherosclerosis 2008 196 : 483 4.
16. Corbett TH, Griswold DP Jr., Roberts BJ, Peckham JC, Schabel FM Jr. Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas. Cancer 1977 40 : 2660 80.
17. Rakkar AN, Katayose Y, Kim M et al. A novel adenoviral vector expressing human Fas/CD95/APO-1 enhances p53-mediated apoptosis. Cell Death Differ 1999 6 : 326 33.
18. Curiel TJ, Coukos G, Zou L et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004 10 : 942 9.
19. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA 1996 275 : 55 60.
20. Rao S, Porter DC, Chen X, Herliczek T, Lowe M, Keyomarsi K. Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proc Natl Acad Sci USA 1999 96 : 7797 802.
21. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 2000 6 : 1399 402.
22. Mach F. Immunosuppressive effects of statins. Atheroscler Suppl 2002 3 : 17 20.
23. Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 2005 4 : 977 87.
24. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003 299 : 1057 61.
25. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003 4 : 337 42.
26. Hinz S, Pagerols-Raluy L, Oberg HH et al. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res 2007 67 : 8344 50.
27. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005 22 : 329 41.
28. Yagi H, Nomura T, Nakamura K et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol 2004 16 : 1643 56.
29. Levings MK, Bacchetta R, Schulz U, Roncarolo MG. The role of IL-10 and TGF-beta in the differentiation and effector function of T regulatory cells. Int Arch Allergy Immunol 2002 129 : 263 76.
30. Taylor MW, Feng GS. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J 1991 5 : 2516 22.
31. Uyttenhove C, Pilotte L, Theate I et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003 9 : 1269 74.
32. Curti A, Pandolfi S, Valzasina B et al. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Blood 2007 109 : 2871 7.
33. Wobser M, Voigt H, Houben R et al. Dendritic cell based antitumor vaccination: impact of functional indoleamine 2,3-dioxygenase expression. Cancer Immunol Immunother 2007 56 : 1017 24.
34. Sakaguchi S. Regulatory T cells: key controllers of immunologic self-tolerance. Cell 2000 101 : 455 8.