PMID- 28248963 OWN - NLM STAT- MEDLINE DCOM- 20170816 LR - 20190208 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 3 DP - 2017 TI - Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is a novel target of lung cancer stem-like cell immunotherapy. PG - e0171460 LID - 10.1371/journal.pone.0171460 [doi] LID - e0171460 AB - 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. FAU - Horibe, Ryota AU - Horibe R AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. AD - Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan. FAU - Hirohashi, Yoshihiko AU - Hirohashi Y AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Asano, Takuya AU - Asano T AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. AD - Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Japan. FAU - Mariya, Tasuku AU - Mariya T AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. AD - Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Japan. FAU - Suzuki, Takeshi AU - Suzuki T AD - Department of Biology, Sapporo Medical University School of Medicine, Japan. FAU - Takaya, Akari AU - Takaya A AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Saijo, Hiroshi AU - Saijo H AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. AD - Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan. FAU - Shionoya, Yosuke AU - Shionoya Y AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. AD - Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan. FAU - Kubo, Terufumi AU - Kubo T AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Nakatsugawa, Munehide AU - Nakatsugawa M AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Kanaseki, Takayuki AU - Kanaseki T AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Tsukahara, Tomohide AU - Tsukahara T AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Watanabe, Kazue AU - Watanabe K AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. AD - MEDICAL and BIOLOGICAL LABORATORIES CO., LTD., Japan. FAU - Atsuyama, Eri AU - Atsuyama E AD - MEDICAL and BIOLOGICAL LABORATORIES CO., LTD., Japan. FAU - Toji, Shingo AU - Toji S AD - MEDICAL and BIOLOGICAL LABORATORIES CO., LTD., Japan. FAU - Hirano, Hiroshi AU - Hirano H AD - Department of Surgical Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Hasegawa, Tadashi AU - Hasegawa T AD - Department of Surgical Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Takahashi, Hiroki AU - Takahashi H AD - Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan. FAU - Sato, Noriyuki AU - Sato N AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. FAU - Torigoe, Toshihiko AU - Torigoe T AD - Department of Pathology, Sapporo Medical University School of Medicine, Japan. LA - eng PT - Journal Article DEP - 20170301 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antigens, Neoplasm) RN - 0 (CTCFL protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (HLA-A2 Antigen) RN - 0 (Neoplasm Proteins) RN - 0 (Peptides) SB - IM MH - Antigens, Neoplasm/genetics/*immunology MH - DNA-Binding Proteins/genetics/*immunology MH - Female MH - HLA-A2 Antigen/genetics/immunology MH - Humans MH - Immunotherapy/*methods MH - K562 Cells MH - Lung Neoplasms/genetics/immunology/pathology/*therapy MH - Male MH - Neoplasm Proteins/genetics/*immunology MH - Neoplastic Stem Cells/*immunology/pathology MH - Peptides/genetics/*immunology PMC - PMC5332062 COIS- Competing Interests: We have the following interests. This study was partly supported by Suharakinenzaidan Co., Ltd. Kazue Watanabe, Eri Atsuyama and Shingo Toji are employees of MEDICAL and BIOLOGICAL LABORATORIES CO., LTD. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2017/03/02 06:00 MHDA- 2017/08/17 06:00 PMCR- 2017/03/01 CRDT- 2017/03/02 06:00 PHST- 2016/06/30 00:00 [received] PHST- 2017/01/21 00:00 [accepted] PHST- 2017/03/02 06:00 [entrez] PHST- 2017/03/02 06:00 [pubmed] PHST- 2017/08/17 06:00 [medline] PHST- 2017/03/01 00:00 [pmc-release] AID - PONE-D-16-26329 [pii] AID - 10.1371/journal.pone.0171460 [doi] PST - epublish SO - PLoS One. 2017 Mar 1;12(3):e0171460. doi: 10.1371/journal.pone.0171460. eCollection 2017.