Advances in augmenting infiltration of active natural killer cells into pediatric and adult solid tumors

Although adoptive natural killer cell therapies have been safe and somewhat effective in hematological malignancies, their performance in solid tumors is hindered by the solid tumor microenvironment, which impairs natural killer cell trafficking and function. Strategies that boost natural killer cell infiltration and maintain their activity in the tumor microenvironment have demonstrated enhanced therapeutic benefits. Multiple strategies have been explored to enhance natural killer cell infiltration and sustain their activity within the tumor microenvironment. These encompass tactics like equipping natural killer cells with chemokine receptors or inducing tumor cells to secrete chemokines to enhance homing, arming natural killer cells with chimeric antigen receptors or concomitant use of natural killer cell engagers to direct natural killer cells to tumors, and blocking immunosuppressive factors such as transforming growth factor-β and immune checkpoints or stimulation by cytokines to make the tumor microenvironment more permissive to natural killer cell function, among others. Here we summarize recent advances in the strategies to augment tumor infiltration of active natural killer cells, aiming to improve natural killer cell-based immunotherapies against pediatric and adult solid tumors.