Department of Medicine, Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
Division of Hematology and Oncology, University of Alabama School of Medicine, Birmingham, AL 35294, United States.
Curr Cancer Drug Targets. 2020;20(7):473-489. doi: 10.2174/1568009620666200502011059.
Over the past decade, our increased understanding of the interactions between the immune system and cancer cells has led to paradigm shifts in the clinical management of solid and hematologic malignancies. The incorporation of immune-targeted strategies into the treatment landscape of acute myeloid leukemia (AML), however, has been challenging. While this is in part due to the inability of the immune system to mount an effective tumor-specific immunogenic response against the heterogeneous nature of AML, the decreased immunogenicity of AML cells also represents a major obstacle in the effort to design effective immunotherapeutic strategies. In fact, AML cells have been shown to employ sophisticated escape mechanisms to evade elimination, such as direct immunosuppression of natural killer cells and decreased surface receptor expression leading to impaired recognition by the immune system. Yet, cellular and humoral immune reactions against tumor-associated antigens (TAA) of acute leukemia cells have been reported and the success of allogeneic stem cell transplantation and monoclonal antibodies in the treatment of AML clearly provides proof that an immunotherapeutic approach is feasible in the management of this disease. This review discusses the recent progress and persisting challenges in cellular immunotherapy for patients with AML.
在过去的十年中,我们对免疫系统和癌细胞之间相互作用的理解不断加深,这导致了实体瘤和血液恶性肿瘤临床管理模式的转变。然而,将免疫靶向策略纳入急性髓系白血病(AML)的治疗方案一直具有挑战性。尽管这部分是由于免疫系统无法针对 AML 的异质性产生有效的肿瘤特异性免疫原性反应,但 AML 细胞的免疫原性降低也是设计有效免疫治疗策略的主要障碍。事实上,AML 细胞已经采用了复杂的逃逸机制来逃避清除,例如直接抑制自然杀伤细胞的免疫功能,以及降低表面受体表达,从而导致免疫系统识别受损。然而,已经有报道称针对急性白血病细胞的肿瘤相关抗原(TAA)存在细胞和体液免疫反应,同种异体干细胞移植和单克隆抗体治疗 AML 的成功清楚地证明了免疫治疗方法在该疾病治疗中的可行性。本综述讨论了 AML 患者细胞免疫治疗的最新进展和持续存在的挑战。