Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts
Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts
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DOI：
10.1182/blood-2009-02-206946
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发表时间：
2009-10-29
期刊：
影响因子：
20.3
通讯作者：
Gribben, John G.
中科院分区：
文献类型：
--
作者：
Le Dieu, Rifca;Taussig, David C.;Gribben, John G.
了解癌症患者的免疫系统如何与恶性细胞相互作用，对于制定成功的免疫策略至关重要。我们研究了新诊断的急性髓性白血病（AML）患者的外周血，以评估这种疾病对患者T细胞的影响。与健康对照相比，AML患者外周血T细胞的绝对数量增加。还观察到CD 3（+）56（+）细胞的绝对数量增加。与健康供体相比，AML患者T细胞的基因表达谱显示了转录的全局差异，表明异常的T细胞活化模式。这些基因表达的变化与慢性淋巴细胞白血病（CLL）中观察到的不同，表明不同肿瘤逃避宿主免疫反应的异质性。然而，与CLL一样，鉴定了参与肌动蛋白细胞骨架形成的差异调节基因，因此评估了AML患者T细胞形成免疫突触的能力。虽然AML T细胞可以与自体母细胞形成缀合物，但它们形成免疫突触和将磷酸酪氨酸信号分子募集到突触的能力显著受损。这些发现确定了AML中的T细胞功能障碍，这可能导致宿主对白血病原始细胞的免疫应答失败。（血。2009;114：3909-3916）
Understanding how the immune system in patients with cancer interacts with malignant cells is critical for the development of successful immunotherapeutic strategies. We studied peripheral blood from newly diagnosed patients with acute myeloid leukemia (AML) to assess the impact of this disease on the patients' T cells. The absolute number of peripheral blood T cells is increased in AML compared with healthy controls. An increase in the absolute number of CD3(+)56(+) cells was also noted. Gene expression profiling on T cells from AML patients compared with healthy donors demonstrated global differences in transcription suggesting aberrant T-cell activation patterns. These gene expression changes differ from those observed in chronic lymphocytic leukemia (CLL), indicating the heterogeneous means by which different tumors evade the host immune response. However, in common with CLL, differentially regulated genes involved in actin cytoskeletal formation were identified, and therefore the ability of T cells from AML patients to form immunologic synapses was assessed. Although AML T cells could form conjugates with autologous blasts, their ability to form immune synapses and recruit phosphotyrosine signaling molecules to the synapse was significantly impaired. These findings identify T-cell dysfunction in AML that may contribute to the failure of a host immune response against leukemic blasts. (Blood. 2009;114:3909-3916)