Long-term consequences of cancer therapy: cognitive impairment following CAR T cell therapy

Abstract

A recent publication by Geraghty et al. in Cell investigates how chimeric antigen receptor (CAR) T cell therapy can induce cognitive impairment in murine models of both central nervous system (CNS)- and non-CNS-based tumors.¹ The authors identified persistent neuroinflammation as a key mechanism underlying these cognitive deficits and successfully explored novel therapeutic strategies, including microglial depletion and CCR3 blockade (Fig. 1).¹

Fig. 1

Temporal overview of onset and duration of side effects following administration of CAR T cell therapy. Compared to more acute toxicities such as CRS and ICANS, cognitive impairment can also be seen after months and years following CAR T cell administration. Underlying mechanisms are characterized by distinct neurobiological alterations such as elevated cerebrospinal fluid (CSF) cytokine and chemokine levels, reduced subcortical oligodendrocyte numbers, and microglial activation. Figure created in BioRender. G., K. (2025)

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