DKK3 attenuates the cytotoxic effect of natural killer cells on CD133+ gastric cancer cells.

Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem-like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D-dependent manner. DKK3 has been demonstrated as a suppressor in many cancers. Interestingly, we found that DKK3 suppressed CD133-induced activation in NK cells by inhibiting Erk pathway and immunological synapse (IS) formation. NK cells-based CSCs immunotherapy may be a novel approach for cancer therapy.