Microglia activation during CAR T cell induced neurotoxicity is dependent on TGF-β-activated kinase-1

Treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) can cause neurotoxicity in patients. The role of microglia in CAR19-induced neurotoxicity was unclear. We observed morphological microglia alterations, increased production of GM-CSF, MCP-1 and TNF by microglia and neurocognitive deficits in B-cell lymphoma-bearing mice upon CAR19 transfer. Gene expression analysis was performed to determine the microglial activation and downstream signalling in response to CAR19 transfer. A20Luc+GFP+ Cells were transplanted to a sub-lethally irradiated BALB/c mice. On Day7, CD19 CAR Tc or NT T cells were transplanted intravenously. On day10, mice were perfused with ice cold PBS, brains were isolated and sorted for CD11b+ and CD45lo cells.