The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM

Profiling of cerebrospinal fluid and tumour samples from patients in a phase 1 trial (NCT05168423) of intracerebroventricular CAR T cells for recurrent glioblastoma indicates that outcomes were defined by remodelling of the patient's own immune landscape rather than by CAR T activation alone, which occurred in every treated patient. Responders were characterised by expansion of cytotoxic natural killer cells, whereas non-responders showed regulatory T cell expansion and abundant baseline immunosuppressive scavenger myeloid cells. The study, published in Cell, is correlative and comes from an early-phase trial: it does not establish causation and reports no comparative survival data, and median survival in glioblastoma remains under 15 months. The authors point to modulation of the host immune compartment as a direction for further research, not as an available treatment.