Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is a novel target of lung cancer stem-like cell immunotherapy

• Published in: PloS one 2017-03, Vol.12 (3), p.e0171460-e0171460
• Main Authors: Horibe, Ryota, Hirohashi, Yoshihiko, Asano, Takuya, Mariya, Tasuku, Suzuki, Takeshi, Takaya, Akari, Saijo, Hiroshi, Shionoya, Yosuke, Kubo, Terufumi, Nakatsugawa, Munehide, Kanaseki, Takayuki, Tsukahara, Tomohide, Watanabe, Kazue, Atsuyama, Eri, Toji, Shingo, Hirano, Hiroshi, Hasegawa, Tadashi, Takahashi, Hiroki, Sato, Noriyuki, Torigoe, Toshihiko
• Format: Article
• Language: English
• Subjects: Antigens; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Biology and Life Sciences; Cancer; Cancer cells; Cancer immunotherapy; Cancer therapies; Care and treatment; Chemotherapy; Cytotoxicity; DNA methylation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - immunology; Eradication; Female; Gene expression; Genetic aspects; Gynecology; Histocompatibility antigen HLA; HLA-A2 Antigen - genetics; HLA-A2 Antigen - immunology; Humans; Immunotherapy; Immunotherapy - methods; K562 Cells; Laboratories; Leukocytes; Lung cancer; Lung carcinoma; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Male; Medical prognosis; Medical research; Medicine; Medicine and Health Sciences; Metastases; Metastasis; mRNA; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Neoplastic Stem Cells - immunology; Neoplastic Stem Cells - pathology; Obstetrics; Pathology; Peptides; Peptides - genetics; Peptides - immunology; Physicians; Polymerase chain reaction; Radiation therapy; Research and Analysis Methods; Tissues
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171460

Lung cancer is one of the most common malignancies with a high rate of mortality. Lung cancer stem-like cells (CSCs)/ cancer-initiating cells (CICs) play major role in resistance to treatments, recurrence and distant metastasis and eradication of CSCs/CICs is crucial to improve recent therapy. Cytotoxic T lymphocytes (CTLs) are major effectors of cancer immunotherapy, and CTLs recognize antigenic peptides derived from antigens that are presented by major histocompatibility complex (MHC) class I molecules. In this study, we analyzed the potency of a cancer-testis (CT) antigen, brother of the regulator of the imprinted site variant subfamily 6 (BORIS sf6), in lung CSC/CIC immunotherapy. BORIS sf6 mRNA was expressed in lung carcinoma cells (9/19), especially in sphere-cultured lung cancer stem-like cells, and in primary lung carcinoma tissues (4/9) by RT-PCR. Immunohistochemical staining using BORIS sf6-specific antibody revealed that high expression of BORIS sf6 is related to poorer prognosis. CTLs could be induced by using a human leukocyte antigen, (HLA)-A2 restricted antigenic peptide (BORIS C34_24(9)), from all of 3 HLA-A2-positive individuals, and CTL clone cells specific for BORIS C34_24(9) peptide could recognize BORIS sf6-positive, HLA-A2-positive lung carcinoma cells. These results indicate that BORIS sf6 is a novel target of lung cancer immunotherapy that might be useful for targeting treatment-resistant lung cancer stem-like cells.