本研究的目的是确定与免疫有关的生物标志物，用于预测免疫治疗（IMT，αCTLA-4 和/或 αPD-1 抗体）和/或去甲基化剂（HMA）在骨髓增生异常综合征（MDS）中的有效抗肿瘤免疫。在第一次治疗前后，对来自 55 名 MDS 患者的外周血样品进行了免疫亚群、 T 细胞受体（TCR）重排、295 个急性髓性白血病（AML）/MDS 相关基因的突变和免疫相关基因表达谱进行了评估。经IMT ± HMA治疗的临床反应者显示中央记忆（CM）CD8+T细胞显著扩张，多样的 TCβ重排治疗前具有增加的克隆性以及初始治疗后新克隆的出现，治疗前突变负荷较高，治疗后随之减少，但不是单独使用HMA患者。TGFβ、自噬和Th1分化途径在治疗后的非反应者中最为下调，而在反应者中则呈上调状态。最后，CTLA-4阻断导致免疫景观的良性变化而PD-1未表现出这种趋势。MDS免疫治疗中肿瘤-免疫景观的分析提供了临床反应生物标志物。© 2023年美国癌症研究协会。

The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA).Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment.Clinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and emergence of novel clones after the initial treatment, and a higher mutation burden pretreatment with subsequent reduction posttreatment. Autophagy, TGFβ, and Th1 differentiation pathways were the most downregulated in nonresponders after treatment, while upregulated in responders. Finally, CTLA-4 but not PD-1 blockade attributed to favorable changes in immune landscape.Analysis of tumor-immune landscape in MDS during immunotherapy provides clinical response biomarkers.©2023 American Association for Cancer Research.