Weaponizing natural killer cells for solid cancer immunotherapy

Enhancing natural killer (NK) cell-based innate immunity has become a promising strategy for immunotherapy against hard-to-cure solid cancers. Monoclonal antibody (mAb) therapy has been used to activate NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC) towards solid cancers. Cancer cells, however, can subvert immunosurveillance using multiple immunosuppressive mechanisms, which may hamper NK cell ADCC. Mechanisms to safely enhance ADCC by NK cells, such as utilizing temporary inhibition of receptor endocytosis to increase antibody presentation from target to effector cells can now be used to enhance NK-cell-mediated ADCC against solid tumors. This review summarizes and discusses the recent advances in the field and highlights current and potential future use of immunotherapies to maximize the therapeutic efficacy of innate anticancer immunity.