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Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer
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 therap...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881150/ https://www.ncbi.nlm.nih.gov/pubmed/33579944 http://dx.doi.org/10.1038/s41467-021-21299-w |
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author | Shin, Hyun Mu Kim, Gwanghun Kim, Sangjib Sim, Ji Hyun Choi, Jiyeob Kim, Minji Kwon, Minsuk Ye, Sang-Kyu Lee, Dong-Sup Cho, Seung Woo Kim, Seung Tae Lee, Jeeyun Kim, Hang-Rae |
author_facet | Shin, Hyun Mu Kim, Gwanghun Kim, Sangjib Sim, Ji Hyun Choi, Jiyeob Kim, Minji Kwon, Minsuk Ye, Sang-Kyu Lee, Dong-Sup Cho, Seung Woo Kim, Seung Tae Lee, Jeeyun Kim, Hang-Rae |
author_sort | Shin, Hyun Mu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7881150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78811502021-02-25 Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer Shin, Hyun Mu Kim, Gwanghun Kim, Sangjib Sim, Ji Hyun Choi, Jiyeob Kim, Minji Kwon, Minsuk Ye, Sang-Kyu Lee, Dong-Sup Cho, Seung Woo Kim, Seung Tae Lee, Jeeyun Kim, Hang-Rae Nat Commun Article 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. Nature Publishing Group UK 2021-02-12 /pmc/articles/PMC7881150/ /pubmed/33579944 http://dx.doi.org/10.1038/s41467-021-21299-w Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Shin, Hyun Mu Kim, Gwanghun Kim, Sangjib Sim, Ji Hyun Choi, Jiyeob Kim, Minji Kwon, Minsuk Ye, Sang-Kyu Lee, Dong-Sup Cho, Seung Woo Kim, Seung Tae Lee, Jeeyun Kim, Hang-Rae Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer |
title | Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer |
title_full | Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer |
title_fullStr | Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer |
title_full_unstemmed | Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer |
title_short | Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer |
title_sort | chromatin accessibility of circulating cd8(+) t cells predicts treatment response to pd-1 blockade in patients with gastric cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881150/ https://www.ncbi.nlm.nih.gov/pubmed/33579944 http://dx.doi.org/10.1038/s41467-021-21299-w |
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