Scholarlink

Background <p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical therapeutic strategy for acute myeloid leukemia (AML). However, relapse remains a major challenge, with limited effective options for managing post-transplant recurrence. Tumor cells escape immune surveillance by establishing a complex, immunosuppressive tumor microenvironment (TME), which plays a central role in immune evasion and disease relapse. Understanding the TME’s impact on immune cells and their functional alterations is therefore of significant clinical importance.</p> Methods <p>Utilizing a non-irradiated AML mouse model and bioinformatic analysis, we systematically analyzed T-cell dynamics during AML progression and identified abnormal metabolic activation in CD8<sup>+</sup> T cells at early disease stages, which correlated with leukemia cell immune evasion.</p> Result <p>We found that when major histocompatibility complex (MHC) molecules on AML cells were haplomatched with immune cells, CD8<sup>+</sup> T cells exhibited robust cytokine and cytotoxic activation, retaining immune profiles similar to those of normal T cells. However, under the same tumor burden, T cells, particularly CD8<sup>+</sup> T cells, showed dramatic metabolic gene activation in MHC-matched leukemic mice. This metabolic activation led to rapid exhaustion of CD8<sup>+</sup> T cells, accelerating leukemia progression. Based on these activated metabolic genes, we established a metabolism-associated genes (MAGs) scoring system. Validation using public datasets revealed that a high MAG score is associated with poor prognosis in AML patients.</p> Conclusions <p>Our findings provide molecular evidence supporting the stronger graft-versus-leukemia effects observed in HLA haploidentical HSCT. Moreover, they highlight that abnormal metabolic activation in CD8<sup>+</sup> T cells during early AML progression contributes to rapid disease advancement and poor prognosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Abnormal metabolic activation of CD8+ T cells correlates with poor prognosis in acute myeloid leukemia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月14日

查看全文
  • Bixia Wang,
  • Jianing Tang,
  • Yang Zhou,
  • Qianqian Huang,
  • Xinya Jiang,
  • Fangqing Zhang,
  • Shuang Fan,
  • Qi Zhang,
  • Jingrui Zhou,
  • Yu Wang,
  • Xiao-Jun Huang,
  • Huidong Guo

摘要

Background

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical therapeutic strategy for acute myeloid leukemia (AML). However, relapse remains a major challenge, with limited effective options for managing post-transplant recurrence. Tumor cells escape immune surveillance by establishing a complex, immunosuppressive tumor microenvironment (TME), which plays a central role in immune evasion and disease relapse. Understanding the TME’s impact on immune cells and their functional alterations is therefore of significant clinical importance.

Methods

Utilizing a non-irradiated AML mouse model and bioinformatic analysis, we systematically analyzed T-cell dynamics during AML progression and identified abnormal metabolic activation in CD8+ T cells at early disease stages, which correlated with leukemia cell immune evasion.

Result

We found that when major histocompatibility complex (MHC) molecules on AML cells were haplomatched with immune cells, CD8+ T cells exhibited robust cytokine and cytotoxic activation, retaining immune profiles similar to those of normal T cells. However, under the same tumor burden, T cells, particularly CD8+ T cells, showed dramatic metabolic gene activation in MHC-matched leukemic mice. This metabolic activation led to rapid exhaustion of CD8+ T cells, accelerating leukemia progression. Based on these activated metabolic genes, we established a metabolism-associated genes (MAGs) scoring system. Validation using public datasets revealed that a high MAG score is associated with poor prognosis in AML patients.

Conclusions

Our findings provide molecular evidence supporting the stronger graft-versus-leukemia effects observed in HLA haploidentical HSCT. Moreover, they highlight that abnormal metabolic activation in CD8+ T cells during early AML progression contributes to rapid disease advancement and poor prognosis.