Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL

CD19 转录组 计算生物学 免疫疗法 计算机科学 生物 免疫学 遗传学 基因 抗原 基因表达 免疫系统
作者
Qiong Zhang,Hui Hu,Si‐Yi Chen,Chunjie Liu,Feifei Hu,Jianming Yu,Yaohui Wu,An‐Yuan Guo
出处
期刊:Genomics, Proteomics & Bioinformatics [Elsevier]
卷期号:17 (2): 190-200 被引量:33
标识
DOI:10.1016/j.gpb.2018.12.008
摘要

Abstract 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.
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