Department of Laboratory Medicine - Laboratory of Haematology, Radboud University Medical Centre, Nijmegen, the Netherlands.
Department of Haematology, Radboud University Medical Centre, Nijmegen, the Netherlands.
Br J Haematol. 2018 Apr;181(1):38-53. doi: 10.1111/bjh.15078. Epub 2018 Jan 9.
New immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long-term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co-inhibitory signalling pathways have been shown to play a crucial role. Via up-regulation of inhibitory checkpoints, tumour-reactive T cell and Natural Killer cell responses can be strongly impeded. Accordingly, the introduction of checkpoint inhibitors targeting CTLA-4 (CTLA4) and PD-1 (PDCD1, CD279)/PD-L1 (CD274, PDCD1LG1) accomplished a breakthrough in cancer treatment, with impressive clinical responses. Numerous new co-inhibitory players and novel combination therapies are currently investigated for their potential to boost anti-tumour immunity and improve survival of cancer patients. Although the challenge here remains to avoid severe systemic toxicity. This review addresses the involvement of co-inhibitory signalling in AML immune evasion and discusses the opportunities for checkpoint blockers in AML treatment.
新的免疫治疗干预措施彻底改变了癌症的治疗方式。异体干细胞移植首次证明了急性髓系白血病 (AML) 的免疫反应能力。此外，还利用了较温和的免疫治疗方法。然而，这些疗法的长期疗效受到各种免疫抵抗和编辑机制的阻碍。在这方面，共抑制信号通路已被证明起着至关重要的作用。通过上调抑制性检查点，可以强烈阻碍肿瘤反应性 T 细胞和自然杀伤细胞的反应。因此，针对 CTLA-4（CTLA4）和 PD-1（PDCD1、CD279）/PD-L1（CD274、PDCD1LG1）的检查点抑制剂的引入在癌症治疗方面取得了突破，临床反应令人印象深刻。目前正在研究许多新的共抑制因子和新的联合疗法，以评估它们在增强抗肿瘤免疫和提高癌症患者生存率方面的潜力。尽管这里的挑战仍然是避免严重的全身毒性。本综述探讨了共抑制信号在 AML 免疫逃逸中的作用，并讨论了检查点阻滞剂在 AML 治疗中的应用。
