Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells

نویسندگان

  • Rena Morita
  • Satoshi Nishizawa
  • Toshihiko Torigoe
  • Akari Takahashi
  • Yasuaki Tamura
  • Tomohide Tsukahara
  • Takayuki Kanaseki
  • Alice Sokolovskaya
  • Vitaly Kochin
  • Toru Kondo
  • Satoshi Hashino
  • Masahiro Asaka
  • Isao Hara
  • Yoshihiko Hirohashi
  • Noriyuki Sato
چکیده

The aim of the present study was to establish cancer stem-like cell/cancer-initiating cell (CSC/CIC)-targeting immunotherapy. The CSC/CIC are thought to be essential for tumor maintenance, recurrence and distant metastasis. Therefore they are reasonable targets for cancer therapy. In the present study, we found that a heat shock protein (HSP) 40 family member, DnaJ (Hsp40) homolog, subfamily B, member 8 (DNAJB8), is preferentially expressed in CSC/CIC derived from colorectal cancer (CRC) cells rather than in non-CSC/CIC. Overexpression of DNAJB8 enhanced the expression of stem cell markers and tumorigenicity, indicating that DNAJB8 has a role in CRC CSC/CIC. A DNAJB8-specific cytotoxic T lymphocyte (CTL) response could be induced by a DNAJB8-derived antigenic peptide. A CTL clone specific for DNAJB8 peptide showed higher killing activity to CRC CSC/CIC compared with non-CSC/CIC, and CTL adoptive transfer into CRC CSC/CIC showed an antitumor effect in vivo. Taken together, the results indicate that DNAJB8 is expressed and has role in CRC CSC/CIC and that DNAJB8 is a novel target of CRC CSC/CIC-targeting immunotherapy.

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عنوان ژورنال:

دوره 105  شماره 

صفحات  -

تاریخ انتشار 2014