Tumor specific expression of survivin-2B in lung cancer as a novel target of immunotherapy

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2005-05, Vol.48 (2), p.281-289
• Main Authors: Ichiki, Yoshinobu, Hanagiri, Takeshi, Takenoyama, Mitsuhiro, Baba, Tetsuro, Fukuyama, Takashi, Nagata, Yoshika, Mizukami, Makiko, So, Tetsuya, Sugaya, Masakazu, Yasuda, Manabu, So, Tomoko, Sugio, Kenji, Yasumoto, Kosei
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm; Biological and medical sciences; Biomarkers; Cancer Vaccines; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - therapy; CTL; Gene Expression Profiling; Humans; Immunity, Cellular; Immunotherapy; Inhibitor of Apoptosis Proteins; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - therapy; Medical sciences; Microtubule-Associated Proteins - biosynthesis; Microtubule-Associated Proteins - immunology; Neoplasm Proteins; Pneumology; Reverse Transcriptase Polymerase Chain Reaction; Survivin; Tumor antigen; Tumor immunity; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2004.10.017

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. (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. 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 × 10 7 in patients with survivin-2B expression (−) lung cancer, however, it was one in 5.0 × 10 6 to 6.0 × 10 6 in those with survivin-2B expression (+) lung cancer. 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.