Indoleamine 2,3-dioxygenase 1 alters the proportions of B cell subpopulations in the microenvironment of acute myeloid leukemia

被引:0
|
作者
Yu Yao [1 ]
Yu-ying Liu [1 ]
Jian-feng Li [2 ]
Yun-shuo Chen [2 ]
Lei Shi [1 ]
Yang Shen [2 ]
Li-li Yang [3 ]
Qing Yang [1 ]
机构
[1] Fudan University,State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences
[2] State Key Laboratory of Medical Genomics,undefined
[3] Shanghai Institute of Hematology,undefined
[4] National Research Center for Translational Medicine at Shanghai,undefined
[5] Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,undefined
[6] State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine,undefined
[7] Tianjin Medical University Cancer Institute and Hospital,undefined
[8] National Clinical Research Center for Cancer,undefined
来源
Molecular Biomedicine | / 6卷 / 1期
关键词
Acute myeloid leukemia (AML); Immunosuppression; Indoleamine 2,3-dioxygenase 1 (IDO1); B cells; IDO1 inhibitors;
D O I
10.1186/s43556-025-00262-x
中图分类号
学科分类号
摘要
Acute myeloid leukemia (AML), the most common leukemia in adults, exhibits immune escape characteristics like solid tumors. The expression of indoleamine 2,3-dioxygenase 1 (IDO1), a well-recognized immune checkpoint, has been detected in AML blast cells and is associated with poor clinical outcome. Although an imbalance of B cell subpopulations exists in AML patients’ bone marrow microenvironment, the role of B cells and their interaction with IDO1 in AML have yet to be elucidated. Herein, with bioinformatic analysis, we found the close correlations between IDO1 expression and survival and B cell subpopulation proportions in AML patients. Further, our investigation into IDO1 expression and activity, B cell subpopulation proportions and immunosuppressive interleukin-10 (IL-10) level in AML cells and clinical samples revealed significant findings. Using a co-culture system of healthy human PBMCs and AML cell lines, we demonstrated that high IDO1 expression in AML cells could alter the proportions of total B, regulatory B and memory B cells, and increased the level of IL-10. Finally, with the IDO1 inhibitor RY103 designed by our laboratory, we found that IDO1 inhibition had good anti-leukemic effect and restored the abnormal proportions of B cell subpopulations in AML mice. Our study is the first to reveal the modulation of IDO1 on B cell subpopulations in AML, making a significant breakthrough in understanding the immune escape mechanisms of AML. Application of IDO1 inhibitor, such as RY103, targeting the imbalance of B cell subpopulations can lead to innovative treatments for AML.
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