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| Status |
Public on Dec 12, 2019 |
| Title |
Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
Tumor-reactive CD8+ tumor infiltrating lymphocytes (TILs) represent a subtype of T cells that could recognize and destroy tumor specifically. Understanding the regulatory mechanism of tumor-reactive CD8+ T cells has important therapeutic implications. Yet the DNA methylation status of this T cell subtype has not been elucidated. In this study, we segregated tumor-reactive and bystander CD8+ TILs, as well as naïve and effector memory CD8+ T cell subtypes as controls from colorectal cancer (CRC) patients, to compare their transcriptome and methylome characteristics. Transcriptome profiling confirmed previous conclusion that tumor-reactive TILs have an exhausted tissue-resident memory signature. Whole-genome methylation profiling identified a distinct methylome pattern of tumor-reactive CD8+ T cells, with tumor-reactive markers (CD39 and CD103) being specifically demethylated. In addition, dynamic changes were observed during the transition of naïve T cells into tumor-reactive CD8+ T cells. Transcription factor (TF) binding motif enrichment analysis identified several immune-related TFs, including three exhaustion-related genes (NR4A1, BATF and EGR2) and VDR, that potentially play important regulatory role in tumor-reactive CD8+ T cells. Our study supports the involvement of DNA methylation in shaping tumor-reactive and bystander CD8+ TILs, and provides a valuable resource for the development of novel DNA methylation markers and future therapeutics.
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| Overall design |
We used whole-genome methylome profiling and RNA-seq to investigate the characteristics of tumor-reactive and bystander CD8+ TILs, as well as naive and effector memory CD8+ T cell subsets as controls from colorectal cancer patients. Raw sequence data access provided at: China Genomic Sequence Archive (GSA) (https://bigd.big.ac.cn/gsa-human/browse/HRA000059) under accession HRA000059.
****Raw sequence data access provided at: China Genomic Sequence Archive (GSA) (https://bigd.big.ac.cn/gsa-human/browse/HRA000059) under accession HRA000059.
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| Contributor(s) |
Yang R, Cheng S, Luo N, Gao R, Yu K, Kang B, Wang L, Zhang Q, Fang Q, Zhang L, Li C, He A, Hu X, Peng J, Ren X, Zhang Z |
| Citation(s) |
31892342 |
| Submission date |
Dec 11, 2019 |
| Last update date |
Mar 12, 2020 |
| Contact name |
Sijin Cheng |
| E-mail(s) |
chengsj@mail.cbi.pku.edu.cn
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| Organization name |
Peking University
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| Department |
School of Life Science
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| Lab |
Zhang Lab
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| Street address |
Haidian District, Beijing Summer Palace Road No. 5
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| City |
Beijing |
| State/province |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (73)
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| Relations |
| BioProject |
PRJNA595032 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE141878_CD8Tcell_raw_counts.csv.gz |
2.1 Mb |
(ftp)(http) |
CSV |
| GSE141878_DN.filt.DMR.bed.gz |
24.5 Kb |
(ftp)(http) |
BED |
| GSE141878_DP.filt.DMR.bed.gz |
33.8 Kb |
(ftp)(http) |
BED |
| GSE141878_EM.filt.DMR.bed.gz |
5.9 Kb |
(ftp)(http) |
BED |
| GSE141878_Naive.filt.DMR.bed.gz |
159.8 Kb |
(ftp)(http) |
BED |
| GSE141878_README.txt |
273 b |
(ftp)(http) |
TXT |
| GSE141878_SP.filt.MDR.bed.gz |
3.1 Kb |
(ftp)(http) |
BED |
| Processed data are available on Series record |
| Raw data not provided for this record |
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