Inhibition of autophagy in cytokine-induced killer cell promotes its cytotoxicity

Due to non-MHC-restricted and potent cytotoxicity against hematological malignancy, one group of heterogeneous effector T cells with diverse TCR specificities, cytokine-induced killer (CIK) cells are considered as a promising therapeutic approach of leukemia. Recently, it has been found that IL-2/IL-15-activated CIK cells were superior to that of generated with IL-2 protocol, however, the underlying mechanism is not fully elucidated. In this study, we found that in IL-2/IL-15-stimulated CIK cells, autophagy was dramatically down-regulated. We produced recombinant lentivirus containing shRNA specific against Beclin 1. Upon knockdown of Beclin 1 in CIK cells, the cytotoxic activity was considerably promoted. Re-expression of Beclin 1 in Beclin 1-knockdown CIK cells compromised their cytotoxic function, confirming that autophagy decreased the cytotoxic function of CIK cells. 3-MA treatment of CIK cells also enhanced their cytotoxic activity, potentially providing possibility to widespread application. Collectively, our study demonstrates autophagy negatively regulates the cytotoxicity of CIK cells on tumor cells, providing a novel approach for promoting the therapeutic efficacy of CIK cells against hematological malignancy.