Wide River Institute of Immunology, Seoul National University, Hongcheon, Republic of Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Nat Commun. 2021 Feb 12;12(1):975. doi: 10.1038/s41467-021-21299-w.
Although tumor genomic profiling has identified small subsets of gastric cancer (GC) patients with clinical benefit from anti-PD-1 treatment, not all responses can be explained by tumor sequencing alone. We investigate epigenetic elements responsible for the differential response to anti-PD-1 therapy by quantitatively assessing the genome-wide chromatin accessibility of circulating CD8 T cells in patients' peripheral blood. Using an assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify unique open regions of chromatin that significantly distinguish anti-PD-1 therapy responders from non-responders. GC patients with high chromatin openness of circulating CD8 T cells are significantly enriched in the responder group. Concordantly, patients with high chromatin openness at specific genomic positions of their circulating CD8 T cells demonstrate significantly better survival than those with closed chromatin. Here we reveal that epigenetic characteristics of baseline CD8 T cells can be used to identify metastatic GC patients who may benefit from anti-PD-1 therapy.
虽然肿瘤基因组分析已经确定了一小部分胃癌（GC）患者从抗 PD-1 治疗中获得了临床获益，但并非所有的反应都可以仅通过肿瘤测序来解释。我们通过定量评估患者外周血循环 CD8 T 细胞的全基因组染色质可及性，研究负责抗 PD-1 治疗反应差异的表观遗传因素。使用转座酶可及染色质测序（ATAC-seq）测定法，我们确定了独特的染色质开放区域，这些区域可显著区分抗 PD-1 治疗的反应者和无反应者。循环 CD8 T 细胞染色质开放性高的 GC 患者在反应者组中明显富集。一致地，在其循环 CD8 T 细胞的特定基因组位置具有高染色质开放性的患者的生存情况明显优于具有封闭染色质的患者。在这里，我们揭示了基线 CD8 T 细胞的表观遗传特征可用于识别可能从抗 PD-1 治疗中获益的转移性 GC 患者。
