Peripheral Blood NK Cells Display Altered Phenotypic and Functional Properties Following Adoptive In-Fusion of Autologous ex vivo Expanded NK Cells

The adoptive infusion of natural killer (NK) cells is a promising immunotherapy for cancer, viral infections, and aging-associated diseases. Clinical responses have been linked to enhanced cytotoxicity and sustained NK cell persistence in vivo. While preconditioning and/or cytokines support improvement in vivo persistence of infused NK cells. However, the effects of ex vivo expanded natural killer (eNK) cells infusion on peripheral blood NK cells-without these interventions-remain unclear. This study analyzed peripheral blood NK cell phenotypes and functions using flow cytometric analysis and Tarascan VP system in healthy subjects. Results showed that autologous eNK cells infusion transiently increased in NK cell proportions and altered subsets and functions. Notably, CD56bright NK cells significantly increased on day 1, accompanied by upregulated expression of activating receptors (NKG2D, NKp30), cytolytic molecules (perforin, granzyme B), and the degranulation marker CD107. By day 7, CD56dim NK cells increased, with significantly enhanced NK cell activity in peripheral blood. These findings indicate that eNK cells infusion induces transient phenotypic and functional changes in peripheral blood NK cells, enhancing their activity in vivo. This study provides insight into optimizing adoptive NK cell therapies to improve therapeutic efficacy.