The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients’ survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.
近年来，具有不同作用机制的新型药物研发显著改变了急性髓系白血病（AML）患者的治疗格局。鉴于免疫系统的显著失调，免疫检查点抑制剂（ICI）为这类患者提供了重要的治疗选择。然而，与在实体瘤中的广泛应用相比，ICI在血液恶性肿瘤中的使用仍然非常有限。本研究分析了AML患者中最具潜力的检查点治疗靶点的表达模式。我们采用流式细胞术分析了72例初治AML患者的外周血样本，评估了CD4+（Th）淋巴细胞和CD33+原始细胞中PD-1、PD-L1、CTLA-4和B7-H3的表达情况。根据治疗结果和细胞遗传学分子风险对患者进行分层分析。结果显示，与完全缓解（CR）患者相比，治疗无应答（NR）患者的Th细胞中PD-1表达频率更高。原始细胞CTLA-4水平降低是区分CR与NR患者的另一因素。PD-1水平升高与患者较差的生存趋势相关。此外，Th淋巴细胞中B7-H3表达频率较高时，AML患者的预后更差。综上所述，本研究揭示了特定ICI作为AML治疗预后预测指标的重要意义，后续需要通过多中心研究对这些数据进行验证。
肿瘤(癌症)患者之家