Bortezomib Augments Natural Killer Cell Targeting of Stem-Like Tumor Cells.

摘要: Tumor cells harboring stem-like/cancer stem cell (CSC) properties have been identified and isolated from numerous hematological solid malignancies. These stem-like tumor can persist following conventional cytoreductive therapies, such as chemotherapy radiotherapy, thereby repopulating the seeding relapse and/or metastasis. We previously shown that natural killer (NK) preferentially target via non- major histocompatibility complex (MHC) restricted mechanisms. Here, we demonstrated proteasome inhibitor, bortezomib, augments NK targeting of cell-like against multiple human tumor-derived cancer lines primary tissue samples. Mechanistically, this was mediated by upregulation surface ligands MHC class I chain-related protein A B (MICA MICB) on aldehyde dehydrogenases (ALDH)-positive CSCs. The increased expression MICA MICB CSC targets enhanced killing in vitro ex vivo both patient-derived xenograft In vivo, combination bortezomib allogeneic adoptive transfer immunodeficient mice led to elimination CSCs well growth delay orthotopic glioblastoma tumors. Taken together, our data support a strategy for potentially improved outcomes clinical patients.