scRNA-seq 揭示复发 T-ALL 中的免疫微环境和 JUN 介导的 NK 细胞耗竭

T cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease characterized by a high relapse rate. By single-cell transcriptome analysis, we characterize the bone marrow immune microenvironment in patients with T-ALL, identifying 13 major cell clusters.

These patients exhibited abnormally expanded hematopoietic stem cells (HSCs) and granulocyte-monocyte progenitors (GMPs), immunosuppressive traits in CD4 + T, CD8 + T, and natural killer (NK) cells. Subdividing CD4 + T cells reveal two subsets transitioning between T helper (Th)1/Th2, Annexin-A1 (ANXA1) - GATA3 - CD4 + T, and ANXA1 + GATA3 + CD4 + T.

Additionally, NK cells demonstrate exhaustion in the tumor microenvironment of patients with relapsed T-ALL, with JUN identified as a critical factor.

Additionally, JUN is also highly expressed in T-ALL and is crucial for maintaining its proliferation. The JUN inhibitor exhibited successful lethality toward leukemia cells and ameliorated NK cell exhaustion in relapsed T-ALL cell line, as well as in cell-derived tumor xenograft (CDX), patient-derived tumor xenograft (PDX), and NOTCH1-mutant mouse models. In summary, our findings enhance the understanding of T-ALL relapse mechanisms and support the development of innovative immunotherapies for patients with relapsed T-ALL.