Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer
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- Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer
- Shin, Hyun Mu; Kim, Gwanghun; Kim, Sangjib; Sim, Ji Hyun; Choi, Jiyeob; Kim, Minji; Kwon, Minsuk; Ye, Sang-Kyu; Lee, Dong-Sup; Cho, Seung Woo; Kim, Seung Tae; Lee, Jeeyun; Kim, Hang-Rae
- Issue Date
- NATURE RESEARCH
- NATURE COMMUNICATIONS, v.12, no.1, pp.975
- 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. Anti-PD-1 therapy could induce a durable response in patients with gastric cancer, however biomarkers to predict response to immunotherapy are generally lacking. Here the authors report that openness of chromatin in circulating CD8(+) T cells predicts treatment outcome in patients with metastatic gastric cancer treated with pembrolizumab.
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