title: Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is a novel target of lung cancer stem-like cell immunotherapy.
abstract: 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.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.|Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Horibe
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.|Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.|Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Mariya
authors.affiliation: Department of Biology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Takaya
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.|Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saijo
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.|Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shionoya
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Munehide
authors.initials: M
authors.lastname: Nakatsugawa
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.|MEDICAL and BIOLOGICAL LABORATORIES CO., LTD., Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: MEDICAL and BIOLOGICAL LABORATORIES CO., LTD., Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Atsuyama
authors.affiliation: MEDICAL and BIOLOGICAL LABORATORIES CO., LTD., Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Toji
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirano
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D020014:K562 Cells; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; D010455:Peptides