Cytokine-mediated increase in endothelial-leukocyte interaction mediates brain capillary plugging during CAR T cell neurotoxicity.

ABSTRACT: CD19-directed CAR T cells treat cancer, but also cause immune effector cell associated neurotoxicity syndrome (ICANS). Despite strong epidemiologic links between cytokine release syndrome and ICANS, it is uncertain how elevated systemic cytokines and activated immune cells cause brain dysfunction. We previously showed that leukocytes plug brain capillaries in an immunocompetent mouse model of CD19-CAR neurotoxicity. Here, we used the same model to explore how integrin activation and endothelial adhesion molecule expression contribute to capillary plugging. In vivo two-photon imaging revealed increased expression of ICAM-1 on brain capillaries, with spatially restricted VCAM-1 increases. TNF, IFN-γ, and IL-1β at concentrations equivalent to CAR T cell patient blood levels upregulated ICAM-1

SUBMITTER: Park L 

PROVIDER: S-EPMC11888194 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature