UCLA

Natural killer (NK) cells are known to play crucial role in halting the progression of cancer. They have the abilities to selectively lyse and differentiate cancer stem cells (CSCs) via direct cytotoxicity and secreted IFN-γ secretion and membrane-bound TNF-α, respectively, which leads to slower tumor growth and limit tumor metastasis. However, lower numbers and functions of NK cells from cancer patients have been reported. This study provides evidences that CD16 receptor but not Toll-like receptor signaling pathway on both NK cells and monocytes from cancer patients is defective resulting the lack of activation in cancer patients, which resulting less differentiation ability of NK cells from cancer patients. In addition, for NK immunotherapy, a methodology to expand and enhance the numbers and functions of NK cells was previously established. The expanded NK cells with potent functions are celled super-charged NK cells. This study investigated the differences of primary and super-charged NK cells and showed that super-charged NK cells have higher level of proliferation markers, more cytokine and chemokine secretion, and more polyfunctional population and are not inactivated after encountering tumor cells. Lastly, it was illustrated that super-charged NK cells preferentially expand CD8+ memory T cells by lysing CD4+ T cells during the expansion process. These compelling findings provides novel approaches for cancer immunotherapy encompassing the stabilization of CD16 receptor on both NK cells and monocytes of cancer patients as well as the possibilities of combination cell adoptive immunotherapy with allogeneic NK and autologous CD8+ T cells.