Olfactory receptor family receptor, family 7, subfamily C, member 1 is a novel marker of colon cancer-initiating cells and is a potent target of immunotherapy.

Purpose: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy. Experimental Design: Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CIC were analyzed by cDNA micro-array and RT-PCR. Protein expression of Olfactory receptor family receptor, family 7, subfamily C, member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene over-expression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by flowcytometer and analyzed. Cytotoxic T lymphocytes (CTLs) specific for OR7C1 peptide were generated, and the anti-tumor effect was addressed by mice adoptive transfer model. Results: OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicty than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific cytotoxic T lymphocytes (CTLs) showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater anti-tumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model. Conclusions: OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy.

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