NK Cell-Based Immunotherapy: Pioneering a New Era in Cancer Treatment

Abstract: Natural killer (NK) cells are essential cytotoxic effectors of the innate immune system with significant therapeutic advantages in cancer immunotherapy, primarily due to their intrinsic MHC-unrestricted cytotoxicity and capacity for antigen-independent tumor recognition. Compared to T cell-based immunotherapies, NK cell-centered strategies facilitate precision immunotherapy through chimeric antigen receptor (CAR) engineering while demonstrating superior allogeneic compatibility. This inherent resistance to graft-versus-host disease (GVHD) circumvents the limitations of autologous cell sourcing and enables “off-the-shelf” therapeutic availability. This review systematically outlines the developmental biology and functional characteristics of NK cells, their diverse cellular origins, and the dynamic regulatory mechanisms governed by the balance of activating and inhibitory receptors. Furthermore, it highlights recent advances in the clinical translation of engineered NK cell therapies, including CAR-NK cells, and discusses their therapeutic applications in cancer treatment.