Despite substantial progress in the diagnostic and therapeutic procedures, acute myeloid leukaemia (AML) still constitutes a significant problem for patients suffering from its relapses. A comprehensive knowledge of the disease’s molecular background has led to the development of targeted therapies, including immune checkpoint inhibitors, and demonstrated beneficial effects on several types of cancer. Here, we aimed to assess in vitro the potential of the immune checkpoint blockage for supporting anti-cancer responses to the AML backbone therapy with cytarabine. PBMCs of AML patients were collected at admission and, following the therapy, eight complete remission (CR) and eight non-responders (NR) subjects were selected. We assessed the effects of the in vitro treatment of the cells with cytarabine and the immune checkpoint inhibitors: anti-CTLA-4, anti-PD-1, anti-PD-L1. The study protocol allowed us to evaluate the viability of the cancer and the immune cells, proliferation status, phenotype, and cytokine release. Anti-PD-L1 antibodies were found to exert the most beneficial effect on the activation of T cells, with a concomitant regulation of the immune balance through Treg induction. There was no direct influence on the blast cells; however, the modulation of the PD-1/PD-L1 axis supported the expansion of lymphocytes. Changes in the response between CR and NR patients might result from the differential expression of PD-1 and PD-L1, with lower levels in the latter group. The tested blockers appear to support the anti-cancer immune responses rather than directly improve the effects of cytarabine. In conclusion, checkpoint proteins’ modulators might improve the anti-cancer responses in the tumour environment.
尽管诊断和治疗手段已取得显著进展，急性髓系白血病（AML）的复发仍是困扰患者的重大难题。随着对该疾病分子背景的全面认识，靶向治疗（包括免疫检查点抑制剂）得以发展，并在多种癌症治疗中展现出积极疗效。本研究旨在通过体外实验评估免疫检查点阻断对阿糖胞苷AML基础疗法的抗癌增效潜力。研究采集AML患者入院时外周血单个核细胞（PBMCs），经治疗后筛选出8例完全缓解（CR）患者与8例无应答（NR）患者样本。通过体外细胞实验，我们评估了阿糖胞苷联合免疫检查点抑制剂（抗CTLA-4、抗PD-1、抗PD-L1）对癌细胞及免疫细胞活力、增殖状态、表型特征及细胞因子释放的影响。研究发现抗PD-L1抗体能最有效激活T细胞，同时通过诱导调节性T细胞（Treg）调控免疫平衡。虽然对原始细胞无直接作用，但PD-1/PD-L1轴调控能促进淋巴细胞扩增。CR与NR患者间的疗效差异可能与PD-1/PD-L1表达水平相关，后者表达量较低。实验表明，检查点抑制剂主要通过增强抗癌免疫应答发挥作用，而非直接提升阿糖胞苷疗效。综上，检查点蛋白调节剂可能改善肿瘤微环境中的抗癌免疫应答。
肿瘤(癌症)患者之家