髓系白血病
状态5
效应器
免疫疗法
癌症研究
白血病
免疫系统
髓样
细胞毒性T细胞
CD8型
T细胞
生物
医学
免疫学
体外
细胞生物学
生物化学
信号转导
作者
Cong Chen,Shuang Liang,Keli Yue,Ning Wu,Zongru Li,Tianhui Dong,Yang Zhang,Liu M,Qian Jiang,Jiangying Liu,Xiao‐Jun Huang
出处
期刊:Cancer Letters
[Elsevier]
日期:2024-04-01
卷期号:587: 216730-216730
被引量:1
标识
DOI:10.1016/j.canlet.2024.216730
摘要
Under the sustained exposure to tumor microenvironment, effector lymphocytes may transform into the suppressive populations. γδ T cells are recognized as a crucial mediator and effector of immune surveillance and thereby a promising candidate for anti-tumor immunotherapy. Emerging clinical studies implicate that some γδ T subsets play an important role in promoting tumor progression. Our previous study identified an abnormal Vδ2+ T cells subset with regulatory features (Reg-Vδ2) in the patients with newly diagnosed acute myeloid leukemia (AML), and demonstrated that Reg-Vδ2 cells significantly suppressed the anti-AML effects of effector Vδ2 cells (Eff-Vδ2). The molecular mechanism underlying the subset transformation of Vδ2 cells remains unclear. Here, we found that the expression and activity of STAT5 were significantly induced in Reg-Vδ2 cells compared with Eff-Vδ2 cells, which was consistent with the differences found in primary Vδ2 cells between AML patients and healthy donors. In-vitro experiments further indicated that STAT5 was required for the induction of Reg-Vδ2 cells. The combined immunophenotypical and functional assays showed that blockage of STAT5 alleviated the immunosuppressive effect of Reg-Vδ2 cells on Eff-Vδ2 cells and enhanced the anti-AML capacity of Vδ2 cells from health donors and AML patients. Collectively, these results suggest that STAT5 acts as a critical regulator in the transformation of effector Vδ2 cells into a subset with immunosuppressive characteristics, providing a potential target for the improvement the efficacy of γδ T cells-based immunotherapy to treat AML and other hematologic malignancies.
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