Temples, M. N.; Lightsey, S.; Conklin, T.; Phelps, E. A.; Sharma, B.

IntroductionNatural killer (NK) cells are a promising tool for cancer immunotherapy, as they can rapidly recognize and kill cancer cells without prior knowledge of tumor-specific antigens while leaving healthy cells unharmed. However, a major challenge in NK cell-based therapies is their inadequate infiltration and function within solid tumors. Advancements in NK cell therapies for solid malignancies require a better understanding of the various factors that influence NK cell migration to and within the tumor microenvironment.\n\nMethodsThe objective of this study was to develop a chemotaxis chip with a tunable 3D hydrogel that enables the spatiotemporal analysis of NK cell migration.\n\nResults/DiscussionBy manipulating the 3D hydrogel or inhibiting key integrin and protease interactions, we found that NK cells heavily relied on protease-dependent migration but could leverage other mechanisms for faster migration. Additionally, when hyaluronic acid, an important extracellular matrix component in tumors, was incorporated into the hydrogel, NK cells migrated faster and farther in the chemotaxis chip.\n\nConclusionThis study establishes a novel migration assay to observe NK cell behavior in real-time, providing a platform for investigating the mechanisms of NK cell migration and identifying strategies to improve NK cell trafficking within solid tumors.