Cui Tu, Irina Buckle, Ingrid Leal Rojas, Gustavo Rodrigues Rossi, David P Sester, Andrew S Moore, Kristen Radford, Camille Guillerey, Fernando Souza-Fonseca-Guimaraes
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The study utilises advanced cytometry to examine how cancer immunosuppressive pathways affect NK cell phenotypic changes in clinical samples.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>In this study, we conducted a high-dimensional examination of the cell surface expression of 16 NK cell receptors in paediatric patients with acute myeloid leukaemia and acute lymphoblastic leukaemia, as well as in samples of non-age matched adult peripheral blood (APB) and umbilical cord blood (UCB). An unsupervised analysis was carried out in order to identify NK cell populations present in paediatric leukaemias.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We observed that leukaemia NK cells clustered together with UCB NK cells and expressed relatively higher levels of the NKG2A receptor compared to APB NK cells. In addition, CD56<sup>dim</sup>CD16<sup>+</sup>CD57<sup>−</sup> NK cells lacking NKG2A expression were mainly absent in paediatric leukaemia patients. 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引用次数: 0
摘要
目标 以自然杀伤细胞（NK）受体为靶点的免疫疗法有望对抗白血病。遗憾的是，改变 NK 细胞表型的癌症免疫抑制机制阻碍了此类方法的成功。本研究利用先进的细胞计量学方法研究癌症免疫抑制途径如何影响临床样本中 NK 细胞表型的变化。 方法 在这项研究中，我们对急性髓性白血病和急性淋巴细胞白血病儿科患者以及非年龄匹配的成人外周血（APB）和脐带血（UCB）样本中 16 种 NK 细胞受体的细胞表面表达进行了高维检测。为了确定儿童白血病中存在的 NK 细胞群，我们进行了无监督分析。 结果 我们观察到白血病 NK 细胞与 UCB NK 细胞聚集在一起，与 APB NK 细胞相比，白血病 NK 细胞表达的 NKG2A 受体水平相对较高。此外，缺乏 NKG2A 表达的 CD56dimCD16+CD57- NK 细胞主要不存在于儿童白血病患者中。然而，在儿童白血病患者中，表达高水平 NKG2A 的 CD56br NK 细胞群的比例很高。研究发现，白血病 NK 细胞上 NKG2A 的表达与其配体的表达呈正相关，这表明 NKG2A-HLA-E 相互作用可能在改变 NK 细胞对白血病细胞的反应中发挥作用。 结论 我们对儿童白血病患者的 NK 细胞群进行了深入分析。这些结果支持开发针对免疫抑制受体（如 NKG2A）的免疫疗法，以增强针对小儿白血病的先天免疫力。
Exploring NK cell receptor dynamics in paediatric leukaemias: implications for immunotherapy and prognosis
Objectives
Immunotherapies targeting natural killer (NK) cell receptors have shown promise against leukaemia. Unfortunately, cancer immunosuppressive mechanisms that alter NK cell phenotype prevent such approaches from being successful. The study utilises advanced cytometry to examine how cancer immunosuppressive pathways affect NK cell phenotypic changes in clinical samples.
Methods
In this study, we conducted a high-dimensional examination of the cell surface expression of 16 NK cell receptors in paediatric patients with acute myeloid leukaemia and acute lymphoblastic leukaemia, as well as in samples of non-age matched adult peripheral blood (APB) and umbilical cord blood (UCB). An unsupervised analysis was carried out in order to identify NK cell populations present in paediatric leukaemias.
Results
We observed that leukaemia NK cells clustered together with UCB NK cells and expressed relatively higher levels of the NKG2A receptor compared to APB NK cells. In addition, CD56dimCD16+CD57− NK cells lacking NKG2A expression were mainly absent in paediatric leukaemia patients. However, CD56br NK cell populations expressing high levels of NKG2A were highly represented in paediatric leukaemia patients. NKG2A expression on leukaemia NK cells was found to be positively correlated with the expression of its ligand, suggesting that the NKG2A-HLA-E interaction may play a role in modifying NK cell responses to leukaemia cells.
Conclusion
We provide an in-depth analysis of NK cell populations in paediatric leukaemia patients. These results support the development of immunotherapies targeting immunosuppressive receptors, such as NKG2A, to enhance innate immunity against paediatric leukaemia.
期刊介绍：
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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