2. Academic Validation
  3. STAT5 is essential for inducing the suppressive subset and attenuate cytotoxicity of Vδ2+ T cells in acute myeloid leukemia

STAT5 is essential for inducing the suppressive subset and attenuate cytotoxicity of Vδ2+ T cells in acute myeloid leukemia

  • Cancer Lett. 2024 Feb 13:587:216730. doi: 10.1016/j.canlet.2024.216730.
Cong Cheng 1,  Shuang Liang 2,  Keli Yue 3,  Ning Wu 4,  Zongru Li 4,  Tianhui Dong 4,  Xinyu Dong 4,  Min Ling 3,  Qian Jiang 4,  Jiangying Liu 5,  Xiao-Jun Huang 6
Affiliations

Affiliations

  • 1 Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (2019RU029), Beijing, China.
  • 2 Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Department of Clinical Laboratory, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, China.
  • 3 Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  • 4 Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
  • 5 Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. Electronic address: [email protected].
  • 6 Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (2019RU029), Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. Electronic address: [email protected].
PMID: 38360140 DOI: 10.1016/j.canlet.2024.216730
Abstract

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.

Keywords

Acute myeloid leukemia; Immunosuppression; STAT5; T cell transformation; γδ T cells.

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  • Cat. No.
    Product Name
    Description
    Target
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  • HY-101853
    98.39%, STAT5 Inhibitor