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, Ji‐Yeob Choi, Minji Kim, Minsuk Kwon, Sang-Kyu Ye, Dong‐Sup Lee, Seung Woo Cho, Seung Tae Kim, Jeeyun Lee, Hang‐Rae Kim
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.