The chromatin accessibility of circulating CD8+ T cells predicts immune-therapeutic response of PD-1 blockade in gastric cancer

We hypothesized that there are distinct signatures in chromatin of circulating CD8+ T cells depending on their response to anti-PD-1 therapy due to their long-term interaction with the internal stimuli, such as with tumor and its microenvironment, and external stimuli, such as with infectious diseases. To identify unique chromatin regions predicting the clinical outcome of PD-1 therapy, we performed an assay for transposase-accessible chromatin sequencing (ATAC-seq) using blood samples of patients enrolled in PD-1 therapy. From the analysis of ATAC-seq data, we identified quantitatively distinct open regions of chromatin that distinguishes responders from non-responders to PD-1 therapy. We demonstrated for the first time that epigenetic characteristics of pre-treatment CD8+ T cells further identifies GC patients who may benefit from immune checkpoint inhibitors (ICIs) in addition to tumor profiling status. Overall design: All CD8+ T cells isolated from blood samples of metastatic gastric cancer patients were used for ATAC-seq