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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 03, 2023 |
| Title |
Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [visium] |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
While regulatory T (Treg) cells are traditionally viewed as professional suppressors of antigen presenting and effector T cells in both autoimmunity and cancer, recent findings of distinct Treg functions in tissue maintenance suggest that their regulatory purview extends to a wider range of cells and is broader than previously assumed. To elucidate tumoral Treg “connectivity” to diverse tumor-supporting accessory cell types, we explored immediate early changes in their single cell transcriptomes upon punctual Treg depletion in experimental lung cancer and injury-induced inflammation. Prior to any notable T cell activation and inflammation, fibroblasts, endothelial and myeloid cells exhibited pronounced changes in their gene expression in both cancer and injury settings. Factor analysis revealed shared Treg-dependent gene programs, foremost, prominent upregulation of VEGF signaling-related genes upon Treg deprivation in either setting, as well as in Treg-poor vs Treg-rich human lung adenocarcinomas. Accordingly, punctual Treg depletion combined with short-term VEGF blockade showed markedly improved control of PD-1 blockade-resistant lung adenocarcinoma progression in mice compared to the corresponding monotherapies, highlighting a promising factor-based querying approach to elucidating novel rational combination treatments of solid organ cancers.
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| Overall design |
Lungs were collected from KrasLSL-G12D/WTTrp53fl/fl Foxp3GFP-DTR (KP-DTR) mice harboring ~3 months old Adenicarcinomas, following 48 hr treatment with Diphteria toxin (DT) to deplete Tregs, or PBS as control. Lungs were perofused and snap-frozen in OCT. All samples were sections with a Cryostat to a thickness of 10um.
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| Contributor(s) |
Glasner A, Rose SA, Sharma R, Gudjonson H, Green J, Rampersaud S, Valdes IK, Schizas M, Dikiy S, Mendoza A, Hu W, Wang Z, Pe'er D, Rudensky AY |
| Citation(s) |
37127830 |
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| Submission date |
Oct 12, 2022 |
| Last update date |
May 04, 2023 |
| Contact name |
Dana Pe'er |
| E-mail(s) |
peerd@mskcc.org
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| Organization name |
Memorial Sloan Kettering Cancer Center
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| Department |
Computational and Systems Biology
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| Street address |
417 E 68th St
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| GSM6634335 |
Lung KP control (PBS 48 hr) sample #A1, visium |
| GSM6634336 |
Lung KP control (PBS 48 hr) sample #B1, visium |
| GSM6634337 |
Lung KP control (PBS 48 hr) sample #C2, visium |
| GSM6634338 |
Lung KP control (PBS 48 hr) sample #D2, visium |
| GSM6634339 |
Lung KP DT (Diphtheria Toxin 48hr) sample #A1, visium |
| GSM6634340 |
Lung KP DT (Diphtheria Toxin 48hr) sample #B1, visium |
| GSM6634341 |
Lung KP DT (Diphtheria Toxin 48hr) sample #C2, visium |
| GSM6634342 |
Lung KP DT (Diphtheria Toxin 48hr) sample #D2, visium |
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| This SubSeries is part of SuperSeries: |
| GSE202159 |
Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies |
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| Relations |
| BioProject |
PRJNA889847 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE215361_Ctrl1_A1_meta.csv.gz |
77.2 Kb |
(ftp)(http) |
CSV |
| GSE215361_Ctrl2_C1_meta.csv.gz |
95.0 Kb |
(ftp)(http) |
CSV |
| GSE215361_DT1_A1_meta.csv.gz |
102.6 Kb |
(ftp)(http) |
CSV |
| GSE215361_DT2_C1_meta.csv.gz |
94.7 Kb |
(ftp)(http) |
CSV |
| GSE215361_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of CSV, H5, JPG, JSON, PNG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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