Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.
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.
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Rena
R
Morita
Satoshi
S
Nishizawa
Toshihiko
T
Torigoe
Akari
A
Takahashi
Yasuaki
Y
Tamura
Tomohide
T
Tsukahara
Takayuki
T
Kanaseki
Alice
A
Sokolovskaya
Vitaly
V
Kochin
Toru
T
Kondo
Satoshi
S
Hashino
Masahiro
M
Asaka
Isao
I
Hara
Yoshihiko
Y
Hirohashi
Noriyuki
N
Sato
D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000276:immunology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C582953:DNAJB8 protein, human; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins
Cancer immunotherapy; DNAJB8; cancer stem-like cell; colorectal cancer; tumor antigen