Tumor specific expression of survivin-2B in lung cancer as a novel target of immunotherapy.
BACKGROUND
Survivin-2B is reported to be specifically expressed in numerous malignant tissues. Furthermore, survivin-2B includes the epitope peptide (survivin-2B(80-88)) which is capable of binding to HLA-A24. In this study, we evaluated whether survivin-2B could be a novel vaccine target against lung cancer.


METHODS
(1) The differences in the survivin-2B expression between 15 sets of lung cancer tissues and normal lung tissues were investigated using RT-PCR. (2) The expression of survivin-2B was further examined in 42 lung cancer tissues, and the relationship between the expression and clinicopathologic factors was analyzed. (3) To compare the frequency of precursor CTL between survivin-2B positive and negative lung cancer patients, surivivin-2B(80-88) peptide-specific CTL were induced from regional lymph node lymphocytes (LNL) of four HLA-A24 (+) lung cancer patients, in whom two showed a positive survivin-2B expression of lung cancer while another two were negative, after stimulation with surivivin-2B(80-88).


RESULTS
Survivin-2B was specifically expressed in lung cancer tissues, and was expressed in 17 of 42 lung cancer tissues (42.9%). Histologically, it was significantly more frequently expressed in squamous cell carcinoma than in adenocarcinoma (p=0.014). The frequency of precursor CTL in LNL was approximately one in 2.0 x 10(7) in patients with survivin-2B expression (-) lung cancer, however, it was one in 5.0 x 10(6) to 6.0 x 10(6) in those with survivin-2B expression (+) lung cancer.


CONCLUSIONS
Survivin-2B was specifically expressed in lung cancer tissue, and found to specifically elicit a cellular immune response in lung cancer patients and therefore it may be a novel candidate for peptide vaccination.
Ichiki
Yoshinobu
Y
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, Kitakyushu 807-8555, Japan. y-ichiki@med.uoeh-u.ac.jp
Hanagiri
Takeshi
T
Takenoyama
Mitsuhiro
M
Baba
Tetsuro
T
Fukuyama
Takashi
T
Nagata
Yoshika
Y
Mizukami
Makiko
M
So
Tetsuya
T
Sugaya
Masakazu
M
Yasuda
Manabu
M
So
Tomoko
T
Sugio
Kenji
K
Yasumoto
Kosei
K
D000951:Antigens, Neoplasm; D015415:Biomarkers; D019496:Cancer Vaccines; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D020869:Gene Expression Profiling; D006801:Humans; D007111:Immunity, Cellular; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000276:immunology*; D009363:Neoplasm Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D015415:Biomarkers; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin