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.
MeSH terms
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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Female
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HLA-A2 Antigen / genetics
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HLA-A2 Antigen / immunology
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Humans
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Immunotherapy / methods*
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K562 Cells
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Lung Neoplasms / genetics
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Lung Neoplasms / immunology
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Lung Neoplasms / pathology
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Lung Neoplasms / therapy*
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Male
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology*
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Neoplastic Stem Cells / immunology*
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Neoplastic Stem Cells / pathology
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Peptides / genetics
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Peptides / immunology*
Substances
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Antigens, Neoplasm
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CTCFL protein, human
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DNA-Binding Proteins
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HLA-A2 Antigen
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Neoplasm Proteins
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Peptides
Grants and funding
This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to NS), program for developing the supporting system for upgrading education and research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to NS), Health and Labor Sciences Research Grants, a grant-in-aid of Ono Cancer Research Fund (to TTo), Suharakinenzaidan Co., Ltd. (to YH), Grants-in-Aid for Regional R&D Proposal-Based Program from Northern Advancement Center for Science & Technology of Hokkaido Japan (to YH and TTo) and the project for development of innovative research on cancer therapeutics from Japan Agency for Medical Research and Development, AMED and MEDICAL and BIOLOGICAL LABORATORIES CO., LTD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MEDICAL and BIOLOGICAL LABORATORIES CO., LTD provided support in the form of salaries for authors KW, EA and ST, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.