CD163(+) 单核细胞与未成熟 CD177(+) 中性粒细胞的协同扩增标志 CD19 CAR-T 细胞治疗后的重度神经毒性

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a major complication after CAR T cell therapy, but its underlying mechanisms remain poorly understood.

We performed longitudinal immune profiling of paired whole blood and serum samples from patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) treated with CD19 CAR T cells. At peak neurotoxicity, high-dimensional mass cytometry and serum proteomics identified the expansion of CD163 + monocytes and immature CD10 low CD101 low neutrophils correlated with elevated serum ST2 and IL-2RA concentrations.

Integrative immune module analysis identified these features among the strongest predictors of ICANS severity. Independent single-cell transcriptomic profiling validated the emergence of immunoregulatory CD163 + monocytes and identified CD177 as a biomarker of ICANS-associated immature neutrophils.

Together, these findings reveal a coordinated myeloid inflammatory network associated with ICANS and nominate candidate biomarkers and therapeutic targets for improving the safety of CAR T cell therapy.