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Cho, Seung Woo
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Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer

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Title
Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer
Author
Shin, Hyun MuKim, GwanghunKim, SangjibSim, Ji HyunChoi, JiyeobKim, MinjiKwon, MinsukYe, Sang-KyuLee, Dong-SupCho, Seung WooKim, Seung TaeLee, JeeyunKim, Hang-Rae
Issue Date
2021-02
Publisher
NATURE RESEARCH
Citation
NATURE COMMUNICATIONS, v.12, no.1, pp.975
Abstract
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.
URI
https://scholarworks.unist.ac.kr/handle/201301/50579
URL
https://www.nature.com/articles/s41467-021-21299-w
DOI
10.1038/s41467-021-21299-w
ISSN
2041-1723
Appears in Collections:
BME_Journal Papers
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