Immunotherapy-related cognitive impairment after CAR T cell therapy in mice by Anna C. Geraghty, Lehi Acosta-Alvarez, instant download

Immunotherapy-related cognitive impairment after CAR T cell therapy in mice by Anna C. Geraghty, Lehi Acosta-Alvarez, instant download

SUMMARYImmunotherapies have revolutionized cancer care for many tumor types, but their potential long-term cognitive impacts are incompletely understood. Here, we demonstrated in mouse models that chimeric antigen receptor (CAR) T cell therapy for both central nervous system (CNS) and non-CNS cancers impaired cognitivefunction and induced a persistent CNS immune response characterized by white matter microglial reactivity,microglial chemokine expression, and elevated cerebrospinal fluid (CSF) cytokines and chemokines. Consequently, oligodendroglial homeostasis and hippocampal neurogenesis were disrupted. Single-nucleussequencing studies of human frontal lobe from patients with or without previous CAR T cell therapy for brainstem tumors confirmed reactive states of microglia and oligodendrocytes following treatment. In mice, transient microglial depletion or CCR3 chemokine receptor blockade rescued oligodendroglial deficits andcognitive performance in a behavioral test of attention and short-term memory function following CART cell therapy. Taken together, these findings illustrate targetable neural-immune mechanisms underlyingimmunotherapy-related cognitive impairment.