Key Findings

• CAR T cell therapy for both CNS and non-CNS cancers can cause cognitive deficits in mice.

• Treatment triggers white matter microglial activation, neuroinflammation, and disrupted oligodendrocyte function, impairing cognition.

• Human brain tissue analysis confirms microglial and oligodendrocyte dysfunction post-CAR T therapy.

• In mice, blocking microglial activity or inhibiting the CCR3 chemokine pathway restores cognitive and cellular function.

Summary
While immunotherapies like CAR T cell therapy have transformed cancer treatment, their long-term cognitive effects remain unclear. Studies in mice reveal that CAR T therapy—whether targeting CNS or non-CNS cancers—induces cognitive decline, persistent neuroinflammation, and white matter microglial reactivity, disrupting oligodendrocyte function and hippocampal neurogenesis. Human brain tissue from CAR T-treated patients shows similar microglial and oligodendrocyte abnormalities. Notably, in mice, transient microglial depletion or CCR3 blockade reverses these deficits, restoring cognitive performance. These findings identify actionable neuroimmune mechanisms behind immunotherapy-related cognitive impairment.
Fulltext link: https://www.cell.com/cell/fulltext/S0092-8674(25)00391-5