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.