title: The forkhead box M1 transcription factor as a candidate of target for anti-cancer immunotherapy.
abstract: The present study attempted to identify a target antigen for immunotherapy for cholangiocarcinoma. Forkhead box M1 (FOXM1) was selected as a candidate antigen based on the data of previous cDNA microarray analysis of clinical samples of cholangiocarcinoma. The level of FOXM1 mRNA was more than 4 times higher in cancer cells in comparison to adjacent normal epithelial cells, in all of 24 samples of cholangiocarcinoma tissues. An immunohistochemical analysis also detected FOXM1 protein in the cancer cells but not in the normal cells. Twenty-three human FOXM1-derived peptides predicted to bind to HLA-A2 were analyzed to determine their ability to induce HLA-A2-restricted T cells in HLA-A2 transgenic mice. FOXM1(362-370) (YLVPIQFPV), FOXM1(373-382) (SLVLQPSVKV), and FOXM1(640-649) (GLMDLSTTPL) peptides primed HLA-A2-restricted cytotoxic T lymphocytes (CTLs) in the HLA-A2 transgenic mice. Human CTL lines reactive to these 3 peptides could also be established from HLA-A2-positive healthy donors and cancer patients. Natural processing of the 3 epitopes from FOXM1 protein was confirmed by specific killing of HLA-A2-positive FOXM1-transfectants by peptide-induced CTLs. FOXM1 is expressed in various types of cancers and it is also functionally involved in oncogenic transformation and the survival of cancer cells. Therefore, FOXM1 may be a suitable target for immunotherapy against various cancers including cholangiocarcinoma.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yokomine
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Irie
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashida
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ikuta
authors.forename: Michiko
authors.initials: M
authors.lastname: Harao
authors.forename: Katsunori
authors.initials: K
authors.lastname: Imai
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nomori
authors.forename: Koji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000628:therapy; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000628:therapy; D018984:Epitopes, T-Lymphocyte; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D012333:RNA, Messenger
references.citation: Nat Rev Cancer. 2002 Jul;2(7):514-20
references.pmid: 12094237
references.citation: Immunol Rev. 2002 Oct;188:22-32
references.pmid: 12445278
references.citation: Oncogene. 2004 Mar 25;23(13):2385-400
references.pmid: 14767473
references.citation: Clin Cancer Res. 2004 Oct 1;10(19):6437-48
references.pmid: 15475430
references.citation: Cancer Res. 2006 Feb 15;66(4):2153-61
references.pmid: 16489016
references.citation: Nat Rev Immunol. 2004 Dec;4(12):941-52
references.pmid: 15573129
references.citation: Cancer Res. 2006 Oct 1;66(19):9731-5
references.pmid: 17018632
references.citation: Lancet. 2005 Oct 8;366(9493):1303-14
references.pmid: 16214602
references.citation: Lancet Oncol. 2001 Sep;2(9):533-43
references.pmid: 11905707
references.citation: Clin Cancer Res. 2004 Dec 15;10(24):8577-86
references.pmid: 15623641
references.citation: Biochem Biophys Res Commun. 2003 Jun 20;306(1):16-25
references.pmid: 12788060
references.citation: Hepatology. 2005 Jan;41(1):5-15
references.pmid: 15690474
references.citation: Am J Pathol. 2003 Sep;163(3):1033-43
references.pmid: 12937144
references.citation: Cancer Sci. 2005 Aug;96(8):498-506
references.pmid: 16108831
references.citation: J Clin Invest. 2007 Jan;117(1):99-111
references.pmid: 17173139
references.citation: Nat Med. 2004 Sep;10(9):909-15
references.pmid: 15340416
references.citation: Cancer Res. 2002 Dec 1;62(23):7012-7
references.pmid: 12460921
references.citation: Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6047-57
references.pmid: 15447989
references.citation: Nat Rev Drug Discov. 2005 May;4(5):399-409
references.pmid: 15864269
references.citation: Cancer Res. 2005 Jun 15;65(12):5181-9
references.pmid: 15958562
references.citation: Oncogene. 2002 Jun 13;21(26):4120-8
references.pmid: 12037668
references.citation: Cancer Res. 2006 Apr 1;66(7):3593-602
references.pmid: 16585184
references.citation: Nat Cell Biol. 2005 Feb;7(2):126-36
references.pmid: 15654331
references.citation: Nucleic Acids Res. 1997 May 1;25(9):1715-9
references.pmid: 9108152
references.citation: Int J Cancer. 2008 Dec 1;123(11):2616-25
references.pmid: 18770861
references.citation: Biochem Biophys Res Commun. 2001 Mar 9;281(4):936-44
references.pmid: 11237751
references.citation: Clin Cancer Res. 2008 Oct 15;14(20):6487-95
references.pmid: 18927288
references.citation: Cancer Res. 2003 Jul 15;63(14):4112-8
references.pmid: 12874015
references.citation: J Virol. 1998 Oct;72(10):8150-7
references.pmid: 9733856
references.citation: Eur J Immunol. 2001 Apr;31(4):1239-46
references.pmid: 11298350
references.citation: Cancer Immunol Immunother. 2001 Mar;50(1):3-15
references.pmid: 11315507
references.citation: Mol Cell Biol. 1997 Mar;17(3):1626-41
references.pmid: 9032290
references.citation: Int Immunol. 2006 Dec;18(12):1737-47
references.pmid: 17077180
references.citation: J Hepatol. 2003 Oct;39(4):559-63
references.pmid: 12971966
references.citation: Hepatology. 2005 Jun;41(6):1339-48
references.pmid: 15880566
references.citation: Hum Pathol. 2004 Mar;35(3):357-66
references.pmid: 15017593
references.citation: Clin Cancer Res. 2006 May 1;12(9):2689-97
references.pmid: 16675560
references.citation: Cancer Res. 2004 Feb 1;64(3):1164-70
references.pmid: 14871853
references.citation: Cancer Res. 2006 Oct 1;66(19):9408-19
references.pmid: 17018595
references.citation: Biochem Biophys Res Commun. 2006 Apr 28;343(1):269-78
references.pmid: 16540092
references.citation: Cancer Res. 2001 Mar 1;61(5):2129-37
references.pmid: 11280777
references.citation: J Cell Sci. 2005 Feb 15;118(Pt 4):795-806
references.pmid: 15671063
references.citation: Cancer Res. 2002 Aug 15;62(16):4773-80
references.pmid: 12183437
references.citation: Cancer Res. 2006 Feb 1;66(3):1712-20
references.pmid: 16452231
references.citation: Eur J Immunol. 1999 Oct;29(10):3112-21
references.pmid: 10540322
references.citation: Clin Cancer Res. 2004 Oct 1;10(19):6612-21
references.pmid: 15475451