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.

中文翻译：

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NKG2A 能够区分小儿急性白血病中表型受到抑制的自然杀伤细胞。

NK 细胞对于早期肿瘤免疫监视很重要。在患有血液系统癌症的患者中，NK 细胞通常存在功能缺陷，并且其受体库表现出失调。急性白血病是儿童中最常见的癌症，我们对前 B 细胞急性淋巴细胞白血病 (BCP-ALL) 患者的 NK 细胞进行了比较表型分析，以确定异常的 NK 细胞表型。对 BCP-ALL 患者在诊断时、治疗期间和治疗结束时匹配的骨髓和血液 NK 细胞中的 NK 细胞表型、成熟和功能进行分析，并与年龄匹配的儿科对照进行比较。几种标志物的表达在患者中存在偏差，但个体间差异较大。采用多参数方法，我们发现 NKG2A 的高表达水平是区分 BCP-ALL 患者与健康对照者 NK 细胞的单一主要标志物。此外，诊断时 BCP-ALL 患者中初始 CD57-NKG2A NK 细胞占主导地位。此外，我们发现驻留骨髓 CXCR6+ NK 细胞中激活受体 DNAM-1 的表达失调。缺乏 DNAM-1 的 CXCR6+ NK 细胞表达 NKG2A，并且具有较低脱颗粒活性的趋势。总之，NKG2A 的高表达在儿科 BCP-ALL 患者的 NK 细胞表型中占主导地位，表明 NKG2A 可以作为该患者群体的治疗目标。