Chromatin accessibility of circulating CD8+ T cells predicts treatment response to PD-1 blockade in patients with gastric cancer

Hyun Mu Shin (), Gwanghun Kim, Sangjib Kim, Ji Hyun Sim, Jiyeob Choi, Minji Kim, Minsuk Kwon, Sang-Kyu Ye, Dong-Sup Lee, Seung Woo Cho, Seung Tae Kim, Jeeyun Lee () and Hang-Rae Kim ()
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Hyun Mu Shin: Wide River Institute of Immunology, Seoul National University
Gwanghun Kim: Seoul National University College of Medicine
Sangjib Kim: Korea University
Ji Hyun Sim: Seoul National University College of Medicine
Jiyeob Choi: Seoul National University College of Medicine
Minji Kim: Seoul National University College of Medicine
Minsuk Kwon: Sungkyunkwan University School of Medicine
Sang-Kyu Ye: Seoul National University College of Medicine
Dong-Sup Lee: Wide River Institute of Immunology, Seoul National University
Seung Woo Cho: Ulsan National Institute of Science and Technology (UNIST)
Seung Tae Kim: Sungkyunkwan University School of Medicine
Jeeyun Lee: Sungkyunkwan University School of Medicine
Hang-Rae Kim: Wide River Institute of Immunology, Seoul National University

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21299-w

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