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

Abstract

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.

• Authors: 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
• Journal: Cancer science (Cancer Sci) Vol. 105 Issue 4 Pg. 389-95 (Apr 2014) ISSN: 1349-7006 [Electronic] England
• PMID: 24450541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• DNAJB8 protein, human
• HSP40 Heat-Shock Proteins
• Molecular Chaperones
• Nerve Tissue Proteins

Topics

• Antigens, Neoplasm (genetics, immunology)
• Biomarkers, Tumor (immunology)
• Cell Line, Tumor
• Colonic Neoplasms (genetics, immunology, therapy)
• Gene Expression Regulation, Neoplastic (immunology)
• HSP40 Heat-Shock Proteins (biosynthesis, genetics)
• Humans
• Immunotherapy
• Molecular Chaperones (biosynthesis, genetics)
• Molecular Targeted Therapy
• Neoplasm Metastasis
• Neoplasm Recurrence, Local (genetics, immunology, therapy)
• Neoplastic Stem Cells (immunology)
• Nerve Tissue Proteins (biosynthesis, genetics)
• T-Lymphocytes, Cytotoxic (immunology)