The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM
Menée à l'aide d'organoïdes ainsi que d'échantillons de liquides céphalo-rachidiens et d'échantillons tumoraux provenant de patients atteints d'un glioblastome récidivant, cette étude détermine les caractéristiques immunitaires endogènes en fonction de la réponse tumorale aux lymphocytes CAR-T puis examine le rôle de l'activation des lymphocytes CAR-T et des cellules immunitaires de l'hôte dans les résultats thérapeutiques
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with a median survival of under 15 months and no effective treatment after recurrence. A recent phase 1 trial of intracerebroventricular bivalent chimeric antigen receptor (CAR) T cells in recurrent GBM, registered at ClinicalTrials.gov (NCT05168423), showed promising responses, including tumor reduction and prolonged survival. However, relapse remains common. We performed in-depth profiling of longitudinal cerebrospinal fluid (CSF) and tumor samples from responders and non-responders to characterize immune dynamics following infusion. Our study reveals that, although CAR T cells activate post infusion across all patients, outcomes were defined by divergent remodeling of the endogenous immune landscape. Cytotoxic natural killer cell expansion characterized responders, whereas regulatory T cell expansion and abundant baseline immunosuppressive scavenger myeloid cells characterized non-responders. These findings indicate that host immune cells play a critical role in CAR T cell therapy for GBM, suggesting that combinatorial strategies modulating the endogenous immune compartment could improve next-generation treatments.
Cell , article en libre accès, 2026