NK细胞对于早期肿瘤免疫监视具有重要作用。在血液肿瘤患者中，NK细胞通常功能缺陷，并出现其受体组合的失调。急性白血病是儿童最常见的癌症类型，本研究对来自前B细胞急性淋巴细胞白血病（BCP-ALL）患者的NK细胞进行了比较的表型分析，以确定异常的NK细胞表型。对诊断时、治疗过程中和治疗结束时的BCP-ALL患者的骨髓和血液NK细胞进行了表型、成熟度和功能分析，并与与年龄相匹配的儿童对照组进行了比较。患者的多个标记物表达有所偏倚，但存在较大的个体间差异。通过多参数方法，我们发现高表达NKG2A是区分BCP-ALL患者和健康对照组中的NK细胞的主要标记物。此外，幼稚CD57-NKG2A NK细胞在BCP-ALL患者的诊断时占主导地位。此外，我们发现驻留于骨髓CXCR6+ NK细胞中的活化受体DNAM-1的表达失调。缺乏DNAM-1的CXCR6+ NK细胞表达NKG2A，并且有较低的脱颗粒活性倾向。总之，NKG2A的高表达占据了儿童BCP-ALL患者的NK细胞表型，表明NKG2A可能成为该患者群体治疗中的靶点。© 作者们2023年发表。由牛津大学出版社代表白细胞生物学学会出版。

NK cells are important for early tumor immune surveillance. In patients with hematological cancers, NK cells are generally functional deficient and display dysregulations in their receptor repertoires. Acute leukemia is the most common cancer in children, and we here performed a comparative phenotypic profiling of NK cells from pre-B cell acute lymphoblastic leukemia (BCP-ALL) patients to identify aberrant NK cell phenotypes. NK cell phenotypes, maturation, and function were analyzed in matched bone marrow and blood NK cells from BCP-ALL patients at diagnosis, during treatment, and at end of treatment and compared to age-matched pediatric controls. Expression of several markers were skewed in patients, but with large inter-individual variations. Undertaking a multi-parameter approach, we found that high expression levels of NKG2A was the single predominant marker distinguishing NK cells in BCP-ALL patients compared to healthy controls. Moreover, naïve CD57-NKG2A NK cells dominated in BCP-ALL patients at diagnosis. Further, we found dysregulated expression of the activating receptor DNAM-1 in resident bone marrow CXCR6+ NK cells. CXCR6+ NK cells lacking DNAM-1 expressed NKG2A and had a tendency for lower degranulation activity. In conclusion, high expression of NKG2A dominates NK cell phenotypes from pediatric BCP-ALL patients, indicating that NKG2A could be targeted in therapies for this patient group.© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology.