Single-cell sequencing unveils T-cell characteristic in acute myeloid leukemia

生物 髓系白血病 CD8型 T细胞 白血病 FOXP3型 癌症研究 人口 细胞毒性T细胞 免疫学 免疫系统 医学 遗传学 环境卫生 体外
作者
Gelan Zhu,Wenjing Lang,Wanbin Fu,Lan Xu,Jiayi Cai,Hua Zhong
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:132: 111927-111927 被引量:2
标识
DOI:10.1016/j.intimp.2024.111927
摘要

Acute myeloid leukemia (AML) presents as a remarkably heterogeneous disease, and the intricate role of various T cell subtypes, including T helper (Th) cells and regulatory T (Treg) cells, in immune dysregulation and the promotion of leukemia cell proliferation and survival is not yet fully understood. In this study, we conducted a comparative analysis of transcriptome profiles in T cells derived from bone marrow samples of three leukemia patients, both before and after treatment, as well as from a relapse sample. This analysis was facilitated through the utilization of single-cell RNA sequencing. The T cell population was subcategorized into CD4 + T cells and CD8 + T cells. Intriguingly, the composition of CD8 + T cells exhibited a relatively stable pattern before and after treatment, while a substantial difference in composition was observed in CD4 + T cells, notably in Th17 and Treg cell populations. Pseudotime trajectory analysis of CD4 + T cell clusters provided further insights into the augmented transition between Th17-like and Treg cells in AML. This transition was characterized by changes in the expression of key genes, including STAT3, CCR6, IL23R, FOXP3, and CTLA4, along their developmental path. An increased cell-to-cell interaction between AML blast cells and all types of T cells appeared to contribute to the restoration of normal T cell proportions. Notably, the LGALS9-CD45 and LGALS9-CD44 pathways emerged as pivotal interactions between blast cells and Treg cells. Our findings unveil an imbalanced differentiation pattern in CD4 + T cells and elucidate the immunosuppressive profiles linked to leukemia cells, thereby enhancing our understanding of CD4 + T cell functionality in the context of AML.
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