UCLA

We have previously demonstrated that natural killer (NK) cells are the primary immune effectors with the ability to mediate selection and differentiation of several different cancer stem cells/undifferentiated tumors via lysis and secreted or membrane-bound IFN-γ and TNF-α, respectively, leading to growth inhibition and curtailment of tumor metastasis. Here, we present an overview of our recent findings on the biology and significance of NK cells in the selection/differentiation of stem-like tumors using in vitro and in vivo studies conducted in the NSG and humanized-BLT mice. To establish the phenotypic and functional differences between primary NK and super-charged NK cells in vitro and in vivo, we analyzed their surface receptors, cytotoxicity, and cytokine secretion in either NK cells culture, NK-tumor co-culture, and CD34+ humanized mouse model condition. In in vitro studies, super-charged NK cells were more polyfunctional. They expressed higher surface receptors, performed higher cytotoxicity, and secreted higher IFN-γ compared to primary NK cells in vitro. When cultured with tumor tissues, super-charged NK cells were also more resistant to immunosuppression by the tumor tissues. Moreover, we observed similar inhibition of tumor growth by super-charged NK cells in the NSG-CD34+ humanized mouse model as we saw in hu-BLT mice. Therefore, due to their indispensable role in targeting cancer stem-like/undifferentiated tumors and various other vital functions of NK cells which are presented in this thesis, NK cells should be placed high in the armamentarium of tumor immunotherapy.