The study investigates the role of integrins in the migration of leukocytes, particularly dendritic cells (DCs), in both two-dimensional (2D) and three-dimensional (3D) environments. Integrins are transmembrane receptors that couple the actomyosin cytoskeleton to the extracellular environment, and their absence in DCs was found to have no significant impact on their migration in 3D, suggesting that integrin-mediated adhesion is not essential for interstitial leukocyte migration. Instead, the migration is driven by the protrusive flow of the leading edge's actin network, supported by squeezing contractions of the trailing edge to propel the nucleus through narrow spaces. This integrin-independent migration is similar to the locomotion of nematode sperm cells, which is driven by treadmilling polymers of major sperm protein. The study also highlights that while integrins are crucial for extravasation from blood vessels, they do not contribute to migration in tissues. The findings provide new insights into the mechanisms of leukocyte migration and suggest that integrins may act as switchable anchors rather than force transducers during locomotion.The study investigates the role of integrins in the migration of leukocytes, particularly dendritic cells (DCs), in both two-dimensional (2D) and three-dimensional (3D) environments. Integrins are transmembrane receptors that couple the actomyosin cytoskeleton to the extracellular environment, and their absence in DCs was found to have no significant impact on their migration in 3D, suggesting that integrin-mediated adhesion is not essential for interstitial leukocyte migration. Instead, the migration is driven by the protrusive flow of the leading edge's actin network, supported by squeezing contractions of the trailing edge to propel the nucleus through narrow spaces. This integrin-independent migration is similar to the locomotion of nematode sperm cells, which is driven by treadmilling polymers of major sperm protein. The study also highlights that while integrins are crucial for extravasation from blood vessels, they do not contribute to migration in tissues. The findings provide new insights into the mechanisms of leukocyte migration and suggest that integrins may act as switchable anchors rather than force transducers during locomotion.