Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8+ T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.

中文翻译：

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B-ALL的CD19-CAR-T免疫疗法的转录组和调控网络分析。

嵌合抗原受体（CAR）T细胞疗法在临床试验中显示出显着的抗肿瘤功效。在这项研究中，我们报道了CD19特异性CAR-T治疗前后四名B细胞急性淋巴细胞性白血病（B-ALL）患者的骨髓细胞转录组谱。CD19-CAR-T治疗显着减少了白血病细胞的数量，三名患者实现了骨髓缓解（最小残留疾病阴性）。CD19-CAR-T疗法对B-ALL的疗效与骨髓中CAR的丰富和免疫细胞亚群（例如CD8 + T细胞和自然杀伤（NK）细胞）呈正相关。此外，CD19-CAR-T治疗主要影响与细胞周期和免疫应答途径相关的基因表达，包括NK细胞介导的细胞毒性和NOD样受体信号通路。监管网络分析显示，作为致癌基因或肿瘤抑制物的microRNA（例如miR-148a-3p和miR-375）可以​​调节编码转录因子（TF；例如JUN和FOS）的基因与组蛋白之间的串扰（例如，参与CD19-CAR-T治疗的HIST1H4A和HIST2H4A）。此外，许多长的非编码RNA表现出与TF或组蛋白（例如FOS和HIST1H4B）的高度共表达，并且与免疫过程有关。这些转录组分析为进一步了解CAR-T免疫疗法功效的基因表达和相关机制提供了重要线索。（例如，JUN和FOS）和参与CD19-CAR-T治疗的组蛋白（例如HIST1H4A和HIST2H4A）。此外，许多长的非编码RNA表现出与TF或组蛋白（例如FOS和HIST1H4B）的高度共表达，并且与免疫过程有关。这些转录组分析为进一步了解CAR-T免疫疗法功效的基因表达和相关机制提供了重要线索。（例如，JUN和FOS）和参与CD19-CAR-T治疗的组蛋白（例如HIST1H4A和HIST2H4A）。此外，许多长的非编码RNA表现出与TF或组蛋白（例如FOS和HIST1H4B）的高度共表达，并且与免疫过程有关。这些转录组分析为进一步了解CAR-T免疫疗法功效的基因表达和相关机制提供了重要线索。