PLoS ONE (Jan 2017)

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

  • Ryota Horibe,
  • Yoshihiko Hirohashi,
  • Takuya Asano,
  • Tasuku Mariya,
  • Takeshi Suzuki,
  • Akari Takaya,
  • Hiroshi Saijo,
  • Yosuke Shionoya,
  • Terufumi Kubo,
  • Munehide Nakatsugawa,
  • Takayuki Kanaseki,
  • Tomohide Tsukahara,
  • Kazue Watanabe,
  • Eri Atsuyama,
  • Shingo Toji,
  • Hiroshi Hirano,
  • Tadashi Hasegawa,
  • Hiroki Takahashi,
  • Noriyuki Sato,
  • Toshihiko Torigoe

DOI
https://doi.org/10.1371/journal.pone.0171460
Journal volume & issue
Vol. 12, no. 3
p. e0171460

Abstract

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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.