Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Clin Cancer Res. 2023 May 15;29(10):1938-1951. doi: 10.1158/1078-0432.CCR-22-2601.
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.
本研究旨在确定免疫相关生物标志物，以预测骨髓增生异常综合征（MDS）患者在免疫治疗（IMT，αCTLA-4 和/或 αPD-1 抗体）和/或低甲基化剂（HMA）治疗期间的抗肿瘤免疫效果。
对 55 例 MDS 患者的外周血样本进行免疫亚群、T 细胞受体（TCR）谱、295 个急性髓系白血病（AML）/MDS 相关基因的突变以及治疗前后免疫相关基因表达谱分析。
接受 IMT ± HMA 治疗但未接受单独 HMA 治疗的临床应答者表现为中央记忆（CM）CD8+T 细胞显著扩增，TCRβ谱多样化，初始治疗后克隆性增加，新克隆出现，治疗前突变负荷较高，治疗后降低。治疗后，非应答者的自噬、TGFβ和 Th1 分化途径下调最为明显，而应答者则上调。最后，CTLA-4 而非 PD-1 阻断导致免疫景观的有利变化。
在 MDS 免疫治疗期间对肿瘤免疫景观进行分析可为临床反应提供生物标志物。
