Introduction and Purposes: Cancer stem-like cells (CSCs) are the subpopulation of cancer cells that have stem-like phenotypes and high capacity for tumor initiation. These cells have a huge impact in the field of cancer therapy since they are resistant to standard chemoradiotherapy and responsible for disease recurrence. We have isolated CSCs by sphere formation assay or side population assay, and analyzed the immunopathological properties of CSCs derived from human solid cancers.Results: We could identify several genes that were characteristic to CSCs. Remarkably, some of them were expressed exclusively in testicles among normal adult organs and involved in spermatogenesis. siRNA-mediated knockdown of these genes caused decreased sphere-forming capacity and in vivo tumorigenicity, indicating that they were involved in the tumor initiation capacity of CSCs. They were highly immunogenic since specific cytotoxic T-cells (CTLs) were efficiently induced from peripheral blood lymphocytes of healthy volunteers as well as cancer patients. The CTLs exerted specific cytotoxicity against CSCs. We named them “Somato-germinomics antigens” in terms of the functioning antigens shared between somatic cancer cells and germ cells.Conclusion: Our data suggest that CSCs might utilize the specific machinery of germ stem cells for their tumor initiation and express immunogenic antigens. However, CSCs preferentially express PD-L1 on the cell surface, therefore escaping from immune surveillance. Based on these findings, we propose an immunotherapeutic strategy targeting CSCs.
Citation Format: Toshihiko Torigoe, Yoshihiko Hirohashi, Tomohide Tsukahara, Takayuki Kanaseki, Munehide Nakatsugawa, Terufumi Kubo, Kochin Vitaly. Somato-germinomics antigens are immunogenic cancer stem cell antigens [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A036.
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