Guangzhou Medical University, Guangzhou, China.
Department of Hematology, Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2024 Sep 25;15:1437726. doi: 10.3389/fimmu.2024.1437726. eCollection 2024.
Leukemia is a prevalent pediatric life-threatening hematologic malignancy with a poor prognosis. Targeting immune checkpoints (ICs) to reverse T cell exhaustion is a potentially effective treatment for leukemia. Tissue resident memory T (T) cells have been found to predict the efficacy of programmed death receptor-1 inhibitor (anti-PD-1) therapy in solid tumors. However, the IC characteristics of T cells in leukemia and their relationship with prognosis remain unclear.
We employed multi-color flow cytometry to evaluate the frequencies of CD103CD4 and CD103CD8 T cells in the peripheral blood (PB) of patients with acute myeloid leukemia and B-cell acute lymphoblastic leukemia compared to healthy individuals. We examined the expression patterns of PD-1 and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) within the circulating CD103 T cell subsets affected by leukemia. To further elucidate the immunological landscape, we assessed the differentiation status of CD103 T cells across various disease states in patients with leukemia.
Our findings showed a significant increase in the frequency of CD103CD8 T cells in the PB of patients with leukemia who had achieved complete remission (CR) compared to those in the and relapsed/refractory (RR) stages. This increase was accompanied by a notable decrease in the expression levels of PD-1 and TIGIT in CD103CD8 T cells in the CR stage. Additionally, our analysis revealed a higher proportion of CD103CD8 T cells in the central memory (TCM) and effector memory (TEM) subsets of the immune profile. Notably, the proportions of CD103 naïve T cells, CD103 TEM, and CD103 terminally differentiated T cells within the CD8 T cell population were significantly elevated in patients with CR compared to those in the /RR stages.
The data indicate that circulating higher frequency of CD103CD8 T cells with lower expression of PD-1 and TIGIT are associated with favorable outcomes in patients with leukemia. This suggests a potential role of T cells in leukemia prognosis and provides a foundation for developing targeted immunotherapies.
白血病是一种常见的危及生命的儿科血液病，预后不良。针对免疫检查点（ICs）以逆转 T 细胞衰竭是治疗白血病的一种潜在有效方法。已经发现组织驻留记忆 T（T）细胞可预测程序性死亡受体-1 抑制剂（抗 PD-1）在实体瘤中的治疗效果。然而，白血病中 T 细胞的 IC 特征及其与预后的关系尚不清楚。
我们采用多色流式细胞术评估了急性髓系白血病（AML）和 B 细胞急性淋巴细胞白血病（B-ALL）患者与健康个体相比外周血（PB）中 CD103CD4 和 CD103CD8 T 细胞的频率。我们检查了受白血病影响的循环 CD103 T 细胞亚群中 PD-1 和 T 细胞免疫受体与免疫球蛋白和 ITIM 结构域（TIGIT）的表达模式。为了进一步阐明免疫学特征，我们评估了白血病患者在不同疾病状态下 CD103 T 细胞的分化状态。
我们的研究结果表明，在达到完全缓解（CR）的白血病患者的 PB 中，CD103CD8 T 细胞的频率明显增加，而在 和复发/难治（RR）阶段则明显减少。这种增加伴随着 CD103CD8 T 细胞中 PD-1 和 TIGIT 表达水平的显著降低。此外，我们的分析揭示了免疫图谱中 CD103CD8 T 细胞在中央记忆（TCM）和效应记忆（TEM）亚群中的比例更高。值得注意的是，与 /RR 阶段相比，CR 患者的 CD8 T 细胞群中 CD103 幼稚 T 细胞、CD103 TEM 和 CD103 终末分化 T 细胞的比例明显升高。
数据表明，循环中具有较低 PD-1 和 TIGIT 表达的较高频率的 CD103CD8 T 细胞与白血病患者的良好结局相关。这表明 T 细胞在白血病预后中的潜在作用，并为开发靶向免疫疗法提供了基础。
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