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

Overview

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.

publication date

  • February 12, 2021

Research

keywords

  • CD8-Positive T-Lymphocytes
  • Chromatin
  • Programmed Cell Death 1 Receptor
  • Stomach Neoplasms

Identity

PubMed Central ID

  • PMC7881150

Scopus Document Identifier

  • 85100853990

Digital Object Identifier (DOI)

  • 10.1038/nmeth.1923

PubMed ID

  • 33579944

Additional Document Info

volume

  • 12

issue

  • 1