Cancer stem-like cells (CSCs) are small subpopulation of cancer cells that contribute to cancer initiation and progression. 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 studied immunopathologic properties of CSCs derived from colon, breast, and gynecologic cancers to develop a novel CSC-targeted immunotherapy. #1 CSC-specific antigens: CSCs express several germ cell-specific genes. Remarkably, some of them were involved in tumor initiation capacity of CSCs and highly immunogenic since specific cytotoxic T-cells (CTLs) were efficiently induced from peripheral blood lymphocytes. The CTLs exerted specific cytotoxicity against CSCs. Adoptive transfer of the CSC-specific CTLs efficiently protected tumor growth in mouse models. #2 Fibroblastic niche of CSCs: Cancer-associated fibroblasts (CAFs) have important roles in tumor microenvironment. CSCs recruited fibroblasts, which enhanced tumor initiation capacity and immune resistance of CSCs. Gene expression analysis revealed that fibroblast growth factor 4 (FGF4) and FGFR2, a receptor for FGF4 were involved in the fibroblastic niche of CSCs. #3 Innate PD-L1 expression of CSCs: Some CSCs constitutively expressed PD-L1 on the cell surface through activation of PI3K/AKT signaling. Based on these unique properties of CSCs, we propose immunotherapeutic and immunoprophylactic strategy targeting CSCs.

Citation Format: Toshihiko Torigoe, Yoshihiko Hirohashi. Novel immunotherapeutic strategy based on the immunopathologic properties of cancer stem cells [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B135.