Department of Hematology, The First Hospital of Jilin University, Changchun, China.
Norman Bethune Health Science Center of Jilin University, Changchun, China.
Crit Rev Oncol Hematol. 2018 Feb;122:123-132. doi: 10.1016/j.critrevonc.2017.12.013. Epub 2018 Jan 3.
Myelodysplastic syndrome (MDS) is a heterogeneous hematological malignancy, characterized by cytopenia and accompanied by a risk of transformation into acute myeloid leukemia (AML). Epidemiological studies for decades have shown association between autoimmune diseases (AIDs) and MDS. Specifically, patients with antecedent AIDs tends to have an increased risk of developing MDS, and these patients display different clinical characteristics and outcomes. Importantly, immune dysregulation has been the common driving force between MDS and AIDs pathogenesis. Both innate and adaptive immune systems are overly active in the hematopoietic niche of MDS. It has been observed that in addition to many cytokines secreted in the bone marrow (BM) microenvironment, almost all types of immune cells and their downstream signaling pathways participate in MDS pathogenesis and evolution. Currently, growth factor therapy and hypomethylating agents (HMAs), along with supportive care, are the mainstay for MDS treatment. As information about the contribution of immune system has started emerging in different subtypes of MDS, we need to highlight the value of immunomodulatory therapies. Immune activation seems to participate specifically in the development of lower-risk MDS, and therefore, use of immunosuppressive therapies would be an ideal treatment option for this type. However, in high-risk MDS, escape from immune surveillance appears to contribute to its progression, and thus, several immune-activating treatment options, including immune checkpoint inhibitors and vaccines, are being considered. HMAs have been approved for use in treating high-risk MDS for many years based on their cytotoxicity, but since they also display an epigenetic-immunomodulatory role, they can be an option for lower-risk MDS. Thus, in this review, we discuss the immune dysregulation in MDS, including its clinical features, pathogenic mechanism and immunomodulatory therapeutic options.
骨髓增生异常综合征（MDS）是一种异质性血液恶性肿瘤，其特征为血细胞减少，并伴有向急性髓系白血病（AML）转化的风险。几十年来的流行病学研究表明，自身免疫性疾病（AIDs）与 MDS 之间存在关联。具体而言，有前驱 AIDs 的患者发生 MDS 的风险增加，这些患者表现出不同的临床特征和结局。重要的是，免疫失调是 MDS 和 AIDs 发病机制的共同驱动因素。固有和适应性免疫系统在 MDS 的造血龛中过度活跃。人们观察到，除了骨髓（BM）微环境中分泌的许多细胞因子外，几乎所有类型的免疫细胞及其下游信号通路都参与了 MDS 的发病机制和演变。目前，生长因子治疗和低甲基化剂（HMAs）以及支持性护理是 MDS 治疗的主要方法。随着免疫系统的作用信息在不同亚型的 MDS 中开始出现，我们需要强调免疫调节疗法的价值。免疫激活似乎特别参与低危 MDS 的发生，因此，免疫抑制治疗可能是该类型的理想治疗选择。然而，在高危 MDS 中，逃避免疫监视似乎有助于其进展，因此，正在考虑几种免疫激活治疗选择，包括免疫检查点抑制剂和疫苗。HMAs 多年来因其细胞毒性而被批准用于治疗高危 MDS，但由于它们还具有表观遗传免疫调节作用，因此也可作为低危 MDS 的选择。因此，在这篇综述中，我们讨论了 MDS 中的免疫失调，包括其临床特征、发病机制和免疫调节治疗选择。
