The forkhead box M1 transcription factor as a candidate of target for anti-cancer immunotherapy.
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.
Yokomine
Kazunori
K
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Senju
Satoru
S
Nakatsura
Tetsuya
T
Irie
Atsushi
A
Hayashida
Yuki
Y
Ikuta
Yoshiaki
Y
Harao
Michiko
M
Imai
Katsunori
K
Baba
Hideo
H
Iwase
Hirotaka
H
Nomori
Hiroaki
H
Takahashi
Koji
K
Daigo
Yataro
Y
Tsunoda
Takuya
T
Nakamura
Yusuke
Y
Sasaki
Yutaka
Y
Nishimura
Yasuharu
Y
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*
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
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