Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia
Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia
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单细胞转录组分析揭示了难治性原发性浆细胞白血病患者的 BCMA CAR-T 细胞动力学
DOI：
10.1016/j.ymthe.2020.11.028
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发表时间：
2021-02-03
影响因子：
12.4
通讯作者：
Hu, Yongxian
中科院分区：
文献类型：
--
作者：
Li, Xue;Guo, Xin;Hu, Yongxian
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
