Natural Killer Cell-Based Immunotherapies Preferentially Target Stem-Like Cells

Cancer stem cells (CSCs) are a small subset of malignant cells which are resistant to chemo- and radiotherapies and are able to repopulate a tumor after cytoreductive treatments. Radiation therapy on a wide variety of primary solid tumors was shown to preferentially kill non-CSC populations. Natural killer (NK) cells displayed an intrinsic ability to target solid tumor CSCs using ex vivo and in vivo models of human primary tumors and xenografts and this is further enhanced by exposing CSC to irradiation. This is in part due to upregulation of stress-related ligands on the CSC as well as removing the non-CSC populations. Pretreatment of tumor-bearing mice with local radiation resulted in significantly longer survival indicating that radiation therapy in conjunction with immunotherapy targeting CSCs may result in markedly improved anti-tumor effects.;Additionally, similar results were found in normal, non-malignant stem cell types. Embryonic stem cells (ESC) and induced pluripotent stem cells (IPSC) provide great promise to the future of medicine. Because immune rejection represents a major obstacle to the success of all stem cell based therapies, many recent studies have sought to determine the key immune mediators involved in ESC rejection. Murine ESCs were highly sensitive to NK cell attack and showed the most efficient engraftment when recipient animals were depleted of NK cells. Combined, this data suggest that NK cells have an intrinsic ability to target undifferentiated cells and may play an important regulatory role in the suppression of these cell types.