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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月16日

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  • Yu Yao,
  • Yu-ying Liu,
  • Jian-feng Li,
  • Yun-shuo Chen,
  • Lei Shi,
  • Yang Shen,
  • Li-li Yang,
  • Qing Yang

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.