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

作者：Nelson F. Freeburg, Daniel Chafamo, G. Gopikrishna, Regan M. Murphy, Jacqueline J. Peng, Shridhar Parthasarathy, Sydney Dumont, Edward G. Estrada, Meghan Logun, Yusha Sun, Xin Wang, Payal Grover, Jesse L. Rodriguez, Daniel L. Zhang, Kristen Park, Yao Fu, Nadine Benhamouda, Isaias Hernandez-Verdin, Lamia Lamrani, Kelly A. Hicks, Natalie A. Cooper, Christina Ekwegbara, Emma Bawden, Joshua J. Waterfall, Jaime Fuentealba, Marion Alcantara, John T. Seykora, Stephen M. Prouty, David Barrett, Esha Banerjee, Arin Cox, Charles-Antoine Assenmacher, Camilla Macia, Melinda Yin, Erica L. Carpenter, Guo‐li Ming, Catherine Sautès-Fridman, Wolf H. Fridman, Éric Tartour, E. John Wherry, Sebastian Amigorena, Joseph A. Fraietta, MacLean P. Nasrallah, Hongjun Song, Tyler E. Miller, Stephen J. Bagley, Donald M. O’Rourke, Zev A. Binder, Cécile Alanio, Dana Silverbush · 发表于：Cell · 年份：2026 · DOI：10.1016/j.cell.2026.05.026 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Glioma Diagnosis and Treatment、Immune Cell Function and Interaction

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.