Kapoor Sargam, Champion Grace, Basu Aparna, Mariampillai Anu, Olnes Matthew J
Hematology and Medical Oncology, Alaska Native Tribal Health Consortium, 3900 Ambassador Dr., Anchorage, AK 99508, USA.
School of Medicine, University of Washington, 1959 NE Pacific St., Seattle, WA 98195, USA.
Cancers (Basel). 2021 Oct 8;13(19):5026. doi: 10.3390/cancers13195026.
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow. Despite recent advances in treating these diseases, patients with higher-risk MDS and AML continue to have a poor prognosis with limited survival. It has long been recognized that there is an immune component to the pathogenesis of MDS and AML, but until recently, immune therapies have played a limited role in treating these diseases. Immune suppressive therapy exhibits durable clinical responses in selected patients with MDS, but the question of which patients are most suitable for this treatment remains unclear. Over the past decade, there has been remarkable progress in identifying genomic features of MDS and AML, which has led to an improved discernment of the molecular pathogenesis of these diseases. An improved understanding of immune and inflammatory molecular mechanisms of MDS and AML have also recently revealed novel therapeutic targets. Emerging treatments for MDS and AML include monoclonal antibodies such as immune checkpoint inhibitors, bispecific T-cell-engaging antibodies, antibody drug conjugates, vaccine therapies, and cellular therapeutics including chimeric antigen receptor T-cells and NK cells. In this review, we provide an overview of the current understanding of immune dysregulation in MDS and AML and an update on novel immune therapies for these bone marrow malignancies.
骨髓增生异常综合征（MDS）和急性髓系白血病（AML）是起源于骨髓的血液系统恶性肿瘤。尽管近年来在治疗这些疾病方面取得了进展，但高危MDS和AML患者的预后仍然很差，生存期有限。长期以来，人们已经认识到MDS和AML的发病机制中存在免疫成分，但直到最近，免疫疗法在治疗这些疾病中所起的作用仍然有限。免疫抑制疗法在部分MDS患者中表现出持久的临床反应，但哪些患者最适合这种治疗仍不明确。在过去十年中，在确定MDS和AML的基因组特征方面取得了显著进展，这使得对这些疾病分子发病机制的认识有所提高。最近，对MDS和AML免疫及炎症分子机制的进一步了解也揭示了新的治疗靶点。MDS和AML的新兴治疗方法包括单克隆抗体，如免疫检查点抑制剂、双特异性T细胞衔接抗体、抗体药物偶联物、疫苗疗法，以及细胞疗法，包括嵌合抗原受体T细胞和自然杀伤细胞。在本综述中，我们概述了目前对MDS和AML免疫失调的认识，以及这些骨髓恶性肿瘤新型免疫疗法的最新进展。
