title: Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.
abstract: Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone. In this study, we established a novel vaccine procedure in rats, using dendritic cells pulsed with C6 tumor cell lysates in combination with adoptive transfer of T lymphocytes from syngenic donors. On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis. The survival rate of rats bearing C6 glioma was observed. Results showed that the co-immunization strategy had significant anti-tumor potential against the pre-established C6 glioma, and induced a strong cytolytic T lymphocyte response in rats. The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period. Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.
authors: Fuxing Hospital, Capital Medical University, Beijing 100038, China.
authors: Enshan
authors: E
authors: Feng
authors: Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
authors: Haili
authors: H
authors: Gao
authors: Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
authors: Wei
authors: W
authors: Su
authors: Fuxing Hospital, Capital Medical University, Beijing 100038, China.
authors: Chunjiang
authors: C
authors: Yu
keywords: CD4+CD25+FOXP3+ regulatory T cell; adoptive T cell; combined immunotherapy; dendritic cell; glioma
references: Lancet Oncol. 2009 May;10 (5):459-66
references: 19269895
references: Hum Immunol. 2009 May;70(5):294-9
references: 19236900
references: Nat Med. 2001 Jul;7(7):761-5
references: 11433329
references: J Neurooncol. 2005 Aug;74(1):9-17
references: 16078102
references: Nat Genet. 2001 Jan;27(1):18-20
references: 11137992
references: Nat Immunol. 2003 Apr;4(4):330-6
references: 12612578
references: J Exp Med. 2005 Mar 7;201(5):779-91
references: 15753211
references: J Immunol. 2005 Oct 1;175(7):4180-3
references: 16177055
references: J Immunol. 2008 Mar 1;180(5):3122-31
references: 18292535
references: Immunology. 2008 Feb;123(2):157-63
references: 18067556
references: Nat Rev Immunol. 2008 Jan;8(1):59-73
references: 18097448
references: Lancet. 2003 Jan 25;361(9354):323-31
references: 12559880
references: Clin Cancer Res. 2002 Apr;8(4):1021-32
references: 11948109
references: Eur J Immunol. 2009 May;39(5):1323-33
references: 19337997
references: Cancer Res. 2006 Jul 15;66(14):7301-9
references: 16849580
references: Immunol Rev. 2006 Dec;214:229-38
references: 17100888
references: Vaccine. 2009 Oct 19;27(44):6210-6
references: 19699331
references: Clin Cancer Res. 2008 May 15;14(10):3098-104
references: 18483377
references: Front Biosci (Landmark Ed). 2009 Jan 01;14:1761-70
references: 19273160
references: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15806-11
references: 14673094
references: Nat Immunol. 2003 Apr;4(4):337-42
references: 12612581
references: Blood. 2006 Jan 15;107(2):628-36
references: 16179369
references: Cell. 1993 Apr 9;73(1):5-8
references: 8462103
references: Immunity. 2005 Feb;22(2):175-84
references: 15723806
references: Clin Immunol. 2009 Apr;131(1):1-10
references: 19201656
references: Anticancer Res. 2008 Mar-Apr;28(2B):1143-50
references: 18505050
references: Clin Endocrinol (Oxf). 2006 Aug;65(2):215-22
references: 16886963
references: J Neurooncol. 2007 Jun;83(2):145-52
references: 17216339
references: Nat Immunol. 2006 Jan;7(1):83-92
references: 16311599
references: Cancer Res. 2006 Mar 15;66(6):3294-302
references: 16540683
references: Science. 2003 Feb 14;299(5609):1057-61
references: 12522256
references: Hum Immunol. 2008 Apr-May;69(4-5):241-9
references: 18486758
references: Cancer Immunol Immunother. 2008 Jan;57(1):123-31
references: 17522861
references: Immunity. 2008 Jan;28(1):100-11
references: 18199417
references: Curr Opin Immunol. 2008 Apr;20(2):241-6
references: 18508251
references: Immunity. 2008 Jan;28(1):112-21
references: 18199418
references: Immunity. 2008 Sep 19;29(3):372-83
references: 18799145
references: Nat Rev Cancer. 2003 Sep;3(9):666-75
references: 12951585
references: Eur J Immunol. 2003 Feb;33(2):502-11
references: 12645949
references: Brain Pathol. 2009 Oct;19(4):694-712
references: 19744041
references: J Exp Med. 2006 Mar 20;203(3):505-11
references: 16533880
references: Neuro Oncol. 2006 Jul;8(3):261-79
references: 16775224
references: Acta Neuropathol. 2005 Jan;109(1):93-108
references: 15685439
references: Cell Mol Immunol. 2006 Jun;3(3):189-95
references: 16893499
references: PLoS One. 2008 Apr 23;3(4):e1983
references: 18431473
references: Crit Rev Immunol. 2009;29(1):1-42
references: 19348609
references: J Leukoc Biol. 1996 Feb;59(2):196-207
references: 8603992