关键词:
RIBOSOMAL-PROTEINS
CD19
THERAPY
PATHWAY
GENE
摘要:
Chimeric antigen receptor T cell (CAR-T) therapy has revolu-tionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cyto-toxicity in clinical patients remains unexplored. Here, we longi-tudinally profiled the transcriptomes of 55,488 T cells including CAR-T products, CAR-T cells, and endogenous T cells at the peak and remission phases in a plasma cell leuke-mia (PCL) patient treated with BCMA CAR-T cells by single -cell transcriptomic analysis. Our results showed distinct CAR-T and endogenous T cell subsets indicating stage-specific expression in proliferation, cytotoxicity, and intercellular signaling pathways. Furthermore, we found that CAR-T cells at peak phase gradually convert to a highly cytotoxic state from a highly proliferative state along a development trajec-tory. Moreover, re-analysis of a single cell study from CD8+ CD19 CAR-T confirmed our findings. These commonalities suggest conserved mechanisms for CAR-T treatment across he-matological malignancies. Taken together, our current study provides insight into CAR-T cell dynamics during CAR-T ther-apy and proves that both BCMA CAR-T and CD19 CAR-T have similar transcriptional characteristics, especially at the CAR-T peak phase.Y