Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.
Bottom Line: 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 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.
Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.Show MeSH
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Mentions: To verify the immunogenicity for peptides from DNAJB8 protein, DNAJB8-specific CTL were induced using HLA-A*2402-positive healthy volunteer donors. Candidate antigenic peptides carrying the HLA-A*2402-binding anchor motif were screened according to the amino acid sequence of DNAJB8 protein and there were four candidate peptides (DNAJB8_22, DNAJB8_90, DNAJB8_99 and DNAJB8_143) (Fig. 3). The HLA-A24 binding ability was then assessed using a HLA-A24 binding assay with SL8C peptide as a negative control and Survivin-2B_80(9) as a positive control. DNAJB8_22(9), DNAJB8_99(9) and DNAJB8_143(9) showed ability to bind to HLA-A24, whereas DNAJB8_90(10) did not (Fig. 3). Therefore, DNAJB8_22(9), DNAJB8_99(9) and DNAJB8_143(9) peptides were used for further CTL induction experiments.
Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.