Azacitidine differentially affects CD4 pos T-cell polarization in vitro and in vivo in high risk myelodysplastic syndromes

Leukemia Research

Volumn 36, Issue 7, 2012, Pages 921-930

  Bontkes, Hetty J ^a   Ruben, Jurjen M ^a   Alhan, Canan ^a   Westers, Theresia M ^a   Ossenkoppele, Gert J ^a   van de Loosdrecht, Arjan A ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Azacitidine; CD4 T helper cells; Cytokines; IL 17; MDS; Regulatory T cells

Indexed keywords

AZACITIDINE; CD45 ANTIGEN; CD45RO ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 17; INTERLEUKIN 2 RECEPTOR ALPHA; RETINOID RELATED ORPHAN RECEPTOR GAMMA; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR ALPHA;

AGED; ANTIGEN EXPRESSION; ARTICLE; CD3+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DOSE RESPONSE; DRUG RESPONSE; FEMALE; HIGH RISK PATIENT; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MALE; MYELODYSPLASTIC SYNDROME; PATHOGENESIS; POLARIZATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; TH17 CELL; UPREGULATION;

AGED; ANTIGENS, CD3; ANTIMETABOLITES, ANTINEOPLASTIC; AZACITIDINE; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; CELL POLARITY; CELL PROLIFERATION; CELLS, CULTURED; CYTOKINES; HUMANS; MYELODYSPLASTIC SYNDROMES; NEOPLASM STAGING; RISK;

EID: 84862315775     PISSN: 01452126     EISSN: 18735835     Source Type: Journal    
DOI: 10.1016/j.leukres.2012.03.026     Document Type: Article

References (38)

1. Garcia-Manero G. Demethylating agents in myeloid malignancies. Curr Opin Oncol 2008, 20(6):705-710.
2. Pinto A., Zagonel V. 5-Aza-2'-deoxycytidine (Decitabine) and 5-azacytidine in the treatment of acute myeloid leukemias and myelodysplastic syndromes: past, present and future trends. Leukemia 1993, 7(Suppl. 1):51-60.
3. Garcia-Manero G., Fenaux P. Hypomethylating agents and other novel strategies in myelodysplastic syndromes. J Clin Oncol 2011, 29(5):516-523.
4. Goodyear O., Agathanggelou A., Novitzky-Basso I., Siddique S., McSkeane T., Ryan G., et al. Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood 2010, 116:1908-1918.
5. Fenaux P., Mufti G.J., Hellstrom-Lindberg E., Santini V., Gattermann N., Germing U., et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010, 28(4):562-569.
6. Momparler R.L., Bouchard J., Samson J. Induction of differentiation and inhibition of DNA methylation in HL-60 myeloid leukemic cells by 5-AZA-2'-deoxycytidine. Leuk Res 1985, 9(11):1361-1366.
7. Jabbour E., Giralt S., Kantarjian H., Garcia-Manero G., Jagasia M., Kebriaei P., et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer 2009, 115(9):1899-1905.
8. Almstedt M., Blagitko-Dorfs N., Duque-Afonso J.s., Karbach J., Pfeifer D., Jäger E., et al. The DNA demethylating agent 5-aza-2'-deoxycytidine induces expression of NY-ESO-1 and other cancer/testis antigens in myeloid leukemia cells. Leuk Res 2010, 34(7):899-905.
9. Aggarwal S., van de Loosdrecht A.A., Alhan C., Ossenkoppele G.J., Westers T.M., Bontkes H.J. Role of immune responses in the pathogenesis of low-risk MDS and high-risk MDS: implications for immunotherapy. Br J Haematol 2011, 153(5):568-581.
10. Mundle S.D., Ali A., Cartlidge J.D., Reza S., Alvi S., Showel M.M., et al. Evidence for involvement of tumor necrosis factor-alpha in apoptotic death of bone marrow cells in myelodysplastic syndromes. Am J Hematol 1999, 60(1):36-47.
11. Kitagawa M., Saito I., Kuwata T., Yoshida S., Yamaguchi S., Takahashi M., et al. Overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma by bone marrow cells from patients with myelodysplastic syndromes. Leukemia 1997, 11(12):2049-2054.
12. Kordasti S.Y., Afzali B., Lim Z., Ingram W., Hayden J., Barber L., et al. IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome. Br J Haematol 2009, 145(1):64-72.
13. Bouchliou I., Miltiades P., Nakou E., Spanoudakis E., Goutzouvelidis A., Vakalopoulou S., et al. Th17 and FoxP3+ T regulatory cell dynamics and distribution in myelodysplastic syndromes. Clin Immunol 2011, 139:350-359.
14. Kordasti S.Y., Ingram W., Hayden J., Darling D., Barber L., Afzali B., et al. CD4+ CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Blood 2007, 110(3):847-850.
15. Lal G., Zhang N., van der Touw W., Ding Y., Ju W., Bottinger E.P., et al. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol 2009, 182(1):259-273.
16. Yano S., Ghosh P., Kusaba H., Buchholz M., Longo D.L. Effect of promoter methylation on the regulation of IFN-{gamma} gene during in vitro differentiation of human peripheral blood T cells into a Th2 population. J Immunol 2003, 171(5):2510-2516.
17. Polansky J., Kretschmer K., Freyer J., Floess S., Garbe A., Baron U., et al. DNA methylation controls Foxp3 gene expression. Eur J Immunol 2008, 38(6):1654-1663.
18. Sanchez-Abarca L.I., Gutierrez-Cosio S., Santamaria C., Caballero-Velazquez T., Blanco B., Herrero-Sanchez C., et al. Immunomodulatory effect of 5-azacytidine (5-azaC): potential role in the transplantation setting. Blood 2010, 115(1):107-121.
19. Choi J., Ritchey J., Prior J.L., Holt M., Shannon W.D., Deych E., et al. In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia. Blood 2010, 116(1):129-139.
20. Young H.A., Ghosh P., Ye J., Lederer J., Lichtman A., Gerard J.R., et al. Differentiation of the T helper phenotypes by analysis of the methylation state of the IFN-gamma gene. J Immunol 1994, 153(8):3603-3610.
21. Nagar M., Vernitsky H., Cohen Y., Dominissini D., Berkun Y., Rechavi G., et al. Epigenetic inheritance of DNA methylation limits activation-induced expression of FoxP3 in conventional CD25-CD4+ T cells. Int Immunol 2008, 20:1041-1055.
22. Chamuleau M.E.D., van de Loosdrecht A.A., Hess C.J., Janssen J.J.W.M., Zevenbergen A., Delwel R., et al. High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome. Haematologica 2008, 93(12):1894-1898.
23. Allan S.E., Crome S.Q., Crellin N.K., Passerini L., Steiner T.S., Bacchetta R., et al. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol 2007, 19(4):345-354.
24. Chen X., Vodanovic-Jankovic S., Johnson B., Keller M., Komorowski R., Drobyski W.R. Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease. Blood 2007, 110(10):3804-3813.
25. Koyama K., Kagamu H., Miura S., Hiura T., Miyabayashi T., Itoh R., et al. Reciprocal CD4+ T-cell balance of effector CD62Llow CD4+ and CD62LhighCD25+ CD4+ regulatory T cells in small cell lung cancer reflects disease stage. Clin Cancer Res 2008, 14(21):6770-6779.
26. Wieczorek G., Asemissen A.M., Model F., Turbachova I., Floess S., Liebenberg V., et al. Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res 2009, 69:599-608.
27. Kryczek I., Banerjee M., Cheng P., Vatan L., Szeliga W., Wei S., et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 2009, 114(6):1141-1149.
28. Kryczek I., Wei S., Szeliga W., Vatan L., Zou W. Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 2009, 114(2):357-359.
29. Wang L., Yi T., Kortylewski M., Pardoll D.M., Zeng D., Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 2009, 206(7):1457-1464.
30. Murugaiyan G., Saha B. Protumor vs Antitumor Functions of IL-17. J Immunol 2009, 183(7):4169-4175.
31. Nistala K., Adams S., Cambrook H., Ursu S., Olivito B., de J.W., et al. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proc Natl Acad Sci USA 2010, 107(33):14751-14756.
32. Henriques A., Ines L., Pais M.L., da Silva J.A., Paiva A.A. Th17 cells in systemic lupus erythematosus share functional features with Th17 cells from normal bone marrow and peripheral tissues. Clin Rheumatol 2011, http://dx.doi.org/10.1007/s10067-011-1860-9.
33. Annunziato F., Cosmi L., Santarlasci V., Maggi L., Liotta F., Mazzinghi B., et al. Phenotypic and functional features of human Th17 cells. J Exp Med 2007, 204(8):1849-1861.
34. Ganjalikhani Hakemi M., Ghaedi K., Andalib A., Hosseini M., Rezaei A. Optimization of human Th17 cell differentiation in vitro: evaluating different polarizing factors. In Vitro Cell Dev Biol Anim 2011, 47:581-592.
35. Ishida K., Kobayashi T., Ito S., Komatsu Y., Yokoyama T., Okada M., et al. Interleukin-6 gene promoter methylation in rheumatoid arthritis and chronic periodontitis. J Periodontol 2011, http://dx.doi.org/10.1902/jop.2011.110356.
36. Dubovsky J.A., Powers J.J., Gao Y., Mariusso L.F., Sotomayor E.M., Pinilla-Ibarz J.A. Epigenetic repolarization of T lymphocytes from chronic lymphocytic leukemia patients using 5-aza-2'-deoxycytidine. Leuk Res 2011, 35:1193-1199.
37. Hoechst B., Gamrekelashvili J., Manns M.P., Greten T.F., Korangy F. Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells. Blood 2011, 117(24):6532-6541.
38. Koenen H.J.P.M., Smeets R.L., Vink P.M., van Rijssen E., Boots A.M.H., Joosten I. Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 2008, 112(6):2340-2352.