Patients with myelodysplastic neoplasms (MDS) who progress on hypomethylating agents have poor outcomes [1,2,3]. There are no standard treatment approaches in this setting; while high-dose chemotherapy followed by allogeneic stem cell transplant remains a curative option for higher-risk MDS, advanced age and significant comorbidities preclude this approach for many patients [4]. In these cases, novel therapies are urgently needed.

Programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) are upregulated in hypomethylating agent failure MDS [5]. PD-L1 on the surface of MDS cells binds to PD-1 on T cells, facilitating immune evasion [6]. Similarly, CTLA4 on T cells binds to B7 on MDS cells, stifling T-cell receptor activation and contributing to immune escape [7]. These findings provide a rationale for assessing PD-1 and CTLA4 blockade in MDS following hypomethylating agent exposure [7]. Ipilimumab and nivolumab are fully human IgG1k monoclonal antibodies that target CTLA4 and PD-1, respectively [8, 9]. Both monotherapy and combination immunotherapy approaches are safe and effective in solid tumors and lymphomas; however, their safety and efficacy in relapsed or refractory MDS remains unclear.

骨髓增生异常肿瘤（myelodysplastic neoplasms， MDS）患者在低甲基化药物治疗后进展的结局较差[1,2,3]。在这种情况下，没有标准的治疗方法;虽然大剂量化疗后进行同种异体干细胞移植仍然是高危 MDS 的治愈选择，但高龄和严重的合并症使许多患者无法采用这种方法 [4]。在这些情况下，迫切需要新的疗法。

程序性细胞死亡配体 1 （PD-L1） 和细胞毒性 T 淋巴细胞相关蛋白 4 （CTLA4） 在低甲基化试剂失败的 MDS 中上调 [5]。MDS 细胞表面的 PD-L1 与 T 细胞上的 PD-1 结合，促进免疫逃避 [6]。同样，T 细胞上的 CTLA4 与 MDS 细胞上的 B7 结合，抑制 T 细胞受体激活并促进免疫逃逸 [7]。这些发现为评估低甲基化药物暴露后 MDS 中 PD-1 和 CTLA4 阻断提供了理论依据 [7]。Ipilimumab 和 nivolumab 是分别靶向 CTLA4 和 PD-1 的全人 IgG1k 单克隆抗体 [8， 9]。单药治疗和联合免疫治疗方法在实体瘤和淋巴瘤中均安全有效;然而，它们在复发或难治性 MDS 中的安全性和有效性仍不清楚。