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

Cancer Sci. 2014 Apr;105(4):389-95. doi: 10.1111/cas.12362. Epub 2014 Feb 24.

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.

Keywords: Cancer immunotherapy; DNAJB8; cancer stem-like cell; colorectal cancer; tumor antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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