Lenvatinib exacerbates colitis by inhibiting intestinal vascular endothelial MAdCAM-1-mediated B cell trafficking

Here, we demonstrated that Lenv exacerbated both acute and chronic colitis in mouse models by impairing intestinal B cell homeostasis, leading to reduce intestinal B cells and plasma cells, along with decreased IL-10 and IgA secretion.

Mechanistically, Lenv decreased MAdCAM-1 expression in intestinal vascular endothelial cells via the VEGFR/PLCγ/PKC/p65 signaling, thereby disrupting B cell homing to the gut. Notably, blockade of either p65 or MAdCAM-1 abrogated Lenv-induced B cell loss and colitis exacerbation. Furthermore, in both tumor-bearing mice and HCC patients receiving Lenv treatment, decreased serum sMAdCAM-1 levels correlated with reduced serum IgA and disruption of intestinal immune homeostasis.