Cyclophosphamide inhibits the generation and function of CD8 + regulatory T cells

Human Immunology

Volumn 73, Issue 3, 2012, Pages 207-213

  Traverso, Ilaria ^a   Fenoglio, Daniela ^a,b   Negrini, Simone ^a,b   Parodi, Alessia ^a   Battaglia, Florinda ^a   Kalli, Francesca ^a   Conteduca, Giuseppina ^a   Tardito, Samuele ^a   Traverso, Paolo ^a   Indiveri, Francesco ^a,b   Filaci, Gilberto ^a,b  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

Author keywords

CD8 +; Cyclophosphamide; Treg Cancer Autoimmunity

Indexed keywords

4 HYDROXYCYCLOPHOSPHAMIDE; CD28 ANTIGEN; CYCLOPHOSPHAMIDE; PERFOSFAMIDE;

APOPTOSIS; ARTICLE; CD8+ T LYMPHOCYTE; CELL DEATH; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFICACY; DRUG TRANSFORMATION; HUMAN; HUMAN CELL; IN VITRO STUDY; LYMPHOCYTE FUNCTION; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE;

ANTIGENS, CD28; ANTIGENS, CD8; APOPTOSIS; CELL DIFFERENTIATION; CELLS, CULTURED; CYCLOPHOSPHAMIDE; HUMANS; IMMUNE TOLERANCE; IMMUNOTHERAPY, ADOPTIVE; NECROSIS; NEOPLASMS; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY; TUMOR ESCAPE;

EID: 84857111372     PISSN: 01988859     EISSN: 18791166     Source Type: Journal    
DOI: 10.1016/j.humimm.2011.12.020     Document Type: Article

References (40)

1. Sakaguchi S. Regulatory T cells: key controllers of immunologic self-tolerance. Cell 2000, 101:455-458.
2. + T cells in autoimmune disease. Hum Immunol 2008, 69:781-789.
3. Beyer M., Schultze J.L. Regulatory T cells in cancer. Blood 2006, 108:804-811.
4. - T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J Immunol 2007, 179:4323-4334.
5. Keler T., Halk E., Vitale L., O'Neill T., Blanset D., Lee S., et al. Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus macaques. J Immunol 2003, 171:6251-6259.
6. Sansom D.M., Walker L.S. The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology. Immunol Rev 2006, 212:131-148.
7. Graziani G., Tentori L., Navarra P. Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Pharmacol Res 2011, Epub ahead of print.
8. Shevach E.M. From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 2006, 25:195-201.
9. Filaci G., Fenoglio D., Indiveri F. CD8(+) T regulatory/suppressor cells and their relationships with autoreactivity and autoimmunity. Autoimmunity 2011, 44:51-57.
10. Joosten S.A., Ottenhoff T.H. Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination. Hum Immunol 2008, 69:760-770.
11. Sakaguchi S., Wing K., Onishi Y., Prieto-Martin P., Yamaguchi T. Regulatory T cells: how do they suppress immune responses?. Int Immunol 2009, 21:1105-1111.
12. Arnold H., Bourseaux F., Brock N. Chemotherapeutic action of a cyclic nitrogen mustard phosphamide ester (B 518-ASTA) in experimental tumours of the rat. Nature 1958, 181:931.
13. Brock N. The history of the oxazaphosphorine cytostatics. Cancer 1996, 78:542-547.
14. Gomori G. Histochemical demonstration of sites of phosphamidase activity. Proc Soc Exp Biol Med 1948, 69:407-409.
15. Emadi A., Jones R.J., Brodsky R.A. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol 2009, 6:638-647.
16. Bass K.K., Mastrangelo M.J. Immunopotentiation with low-dose cyclophosphamide in the active specific immunotherapy of cancer. Cancer Immunol Immunother 1998, 47:1-12.
17. Brodsky R.A. High-dose cyclophosphamide for autoimmunity and alloimmunity. Immunol Res 2010, 47:179-184.
18. North R.J. Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med 1982, 155:1063-1074.
19. + regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 2004, 34:336-344.
20. Lutsiak M.E., Semnani R.T., De Pascalis R., Kashmiri S.V., Schlom J., Sabzevari H. Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 2005, 105:2862-2868.
21. Motoyoshi Y., Kaminoda K., Saitoh O., Hamasaki K., Nakao K., Ishii N., et al. Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide. Oncol Rep 2006, 16:141-146.
22. + regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 2007, 56:641-648.
23. + T lymphocytes. Clin Exp Immunol 2007, 150:523-530.
24. Diamantstein T., Willinger E., Reiman J. T-suppressor cells sensitive to cyclophosphamide and to its in vitro active derivative 4-hydroperoxycyclophosphamide control the mitogenic response of murine splenic B cells to dextran sulfate. A direct proof for different sensitivities of lymphocyte subsets to cyclophosphamide. J Exp Med 1979, 150:1571-1576.
25. + T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis. J Clin Invest 1995, 95:2711-2719.
26. Wagner T., Heydrich D., Voelcker G., Hohorst H.J. Blood level and urinary excretion of activated cyclophosphamide and its deactivation products in man (author's transl). J Cancer Res Clin Oncol 1980, 96:79-92.
27. Fenoglio D., Ferrera F., Fravega M., Balestra P.C., Battaglia f, Proietti M., et al. Advancements on phenotypic and functional characterization of non-antigen-specific CD8+CD28- regulatory T cells. Hum Immun 2008, 69:745-750.
28. + T reg cells. J Exp Med 2006, 7:1701-1711.
29. Borsellino G., Kleinewietfeld M., Di Mitri D., Sternjak A., Diamantini A., Giometto R., et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 2007, 110:1225-1232.
30. Bernuzzi F., Fenoglio D., Battaglia F., Fravega M., Gershwin M.E., Indiveri F., et al. Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis. J Autoimm 2010, 35:176-180.
31. - T cells and inhibit both T-cell proliferation and CTL function. Hum Immunol 2004, 65:142-156.
32. Dejaco C., Duftner C., Grubeck-Loebenstein B., Schirmer M. Imbalance of regulatory T cells in human autoimmune diseases. Immunology 2006, 117:289-300.
33. Dinesh R.K., Skaggs B.J., La Cava A., Hahn B.H., Singh R.P. CD8+ Tregs in lupus, autoimmunity, and beyond. Autoimmun Rev 2010, 9:560-568.
34. Wolf A.M., Wolf D., Steurer M., Gastl G., Gunsilius E., Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003, 9:606-612.
35. Wang H.Y., Wang R.F. Regulatory T cells and cancer. Curr Opin Immunol 2007, 19:217-223.
36. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006, 6:295-307.
37. Filaci G., Fravega M., Fenoglio D., Rizzi M., Negrini S., Viggiani R., et al. Non-antigen specific CD8+ T suppressor lymphocytes. Clin Exp Med 2004, 4:86-92.
38. Lacki J.K., Mackiewicz S.H., Wiktorowicz K.E. Contrasting effect of oral and intravenous cyclophosphamide treatment on phenotypes of human peripheral blood lymphocytes. Arch Immunol Ther Exp 1994, 42:291-294.
39. +Foxp3+ regulatory T cells. J Immunol 2006, 177:6603-6612.
40. Brode S., Cooke A. Immune-potentiating effects of the chemotherapeutic drug cyclophosphamide. Crit Rev Immunol 2008, 28:109-126.