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GEO help: Mouse over screen elements for information. |
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Status |
Public on Nov 03, 2022 |
Title |
LN-stem, tumor stem, tumor terminally differentiated CD8 T cells from human kidney cancer |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Methylation profiling by high throughput sequencing
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Summary |
This work aimed to understand the source of TCF1+ CD8 T cells in tumors. By studying human tumor draining lymph-nodes (TDLNs), we find that CD8 T cells activate in TDLN but fail to acquire the normal effector program. Instead, these CD8 T cells share functional, transcriptional, and epigenetic traits with TCF1+ stem-like cells in the tumor. This suggests that these activated cells are a precursor to the stem-like CD8 T cells in tumors. By using mouse models, we show that tumor-specific CD8 T cells are activated in TDLN, but do not acquire an effector phenotype. These cells then migrate into the tumor where they require additional co-stimulation from antigen presenting cells to acquire the effector program. This is strikingly different from canonical CD8 T cell activation to acute viruses, where the effector program is acquired immediately. This model of T cell differentiation has important implications to improve immunotherapy.
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Overall design |
CD8 T cell populations were sorted from human PBMCs, lymph nodes, and tumor. RNA was extracted using qiagen micro all-prep columns. RNA was sequenced on an Illumina Hiseq 3000
Cell sorting was performed byFACS Aria II (BD Biosciences). For scRNA-seq (10x) of mouse samples live, CD3-CD19-Ly6G+ I-A/I-E+ cells were sorted from naïve LN, tumor-draining LN, and TRAMPC1-GP tumors. For human scRNA-seq (10x) fresh kidney tumors were used, antigen-presenting cells were sorted as live, CD45+, CD3-, HLADR+
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Contributor(s) |
Prokhnevska N, Kissick H |
Citation missing |
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Submission date |
Oct 27, 2022 |
Last update date |
Jan 04, 2023 |
Contact name |
Haydn Kissick |
E-mail(s) |
haydn.kissick@emory.edu
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Phone |
6172598364
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Organization name |
Emory University
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Street address |
1462 Clifton Rd
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City |
Atlanta |
State/province |
Georgia |
ZIP/Postal code |
30322 |
Country |
USA |
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Platforms (4)
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GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (67)
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Relations |
BioProject |
PRJNA895063 |
Supplementary file |
Size |
Download |
File type/resource |
GSE216731_Human_meth_data.xlsx |
194.0 Mb |
(ftp)(http) |
XLSX |
GSE216731_Mouse_methylation_data.xlsx |
58.1 Mb |
(ftp)(http) |
XLSX |
GSE216731_Prokhnevska_Human_Raw_Counts.csv.gz |
839.2 Kb |
(ftp)(http) |
CSV |
GSE216731_Prokhnevska_MouseRNA_Counts.csv.gz |
997.0 Kb |
(ftp)(http) |
CSV |
GSE216731_RAW.tar |
59.0 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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