CELL INTELLIGENCE · 肿瘤细胞治疗研究

Anti-CD19 Chimeric Antigen Receptor (CAR)-T cell therapies have shown promise for treating B cell malignancies, but the clinical outcome is influenced by both the CAR-T product and the patient's immune system. The role of T cells in the context of CAR-T cell therapy remains poorly understood. This study investigates the transcriptional heterogeneity, clonal expansion and dynamics of T cells in patients undergoing anti-CD19 CAR-T cell therapy. Longitudinal single cell multi-omics analysis was performed on T cells from four patients receiving anti-CD19 CAR-T cell therapy. Single cell RNA-seq, antibody-based protein profiling (AbSeq) and full-length TCR sequences revealed clonally expanded populations displaying plasticity in T cell differentiation, and temporal dynamics of large clones, suggesting ongoing expansion and differentiation. Clonally expanded T cells had heterogeneous gene expression profiles, occupying seven transcriptionally distinct clusters. Analysis of chemokine markers indicated cluster-specific homing tendencies of circulating T cells to peripheral tissues. We found unexpectedly high frequencies of V 1 and V 3 cells in the blood with distinct gene and protein expression profiles. This analysis provides insights into the dynamic and heterogeneous nature of T cells following anti-CD19 CAR-T cell therapy, contributing valuable information for optimizing CAR-T cell therapies in B cell malignancies.