Dasatinib reversibly disrupts T cell motility and activation in lymph nodes.

The tyrosine kinase inhibitor dasatinib is prescribed as a first-line treatment for Philadelphia chromosome-positive leukemias and is increasingly used in other clinical settings. While dasatinib is effective and generally well tolerated, patients often experience a transient lymphocytosis attributable to a dasatinib-induced spleen contraction and an acute mobilization of splenocytes, as we have recently demonstrated in murine models and human patients. In contrast, the impact of dasatinib on lymphocyte surveillance of other secondary lymphoid organs, such as peripheral lymph nodes (LNs), has remained unclear. Here, we report that while dasatinib treatment selectively disrupted in vitro chemotaxis of B but not T cells, it caused a substantial, transient reduction of the in vivo interstitial motility in both subsets. The broad in vivo inhibition of T and B cell motility correlated with dasatinib-induced vasoconstriction of blood vessels and increased hypoxia within LNs. Pharmacological inhibition of the contraction-promoting factor Rho-associated coiled-coil kinase (ROCK) reversed dasatinib-induced LN hypoxia and rescued CD8