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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 03, 2016 |
| Title |
T cell oxygen-sensing proteins establish an immunologically tolerant metastatic niche |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung, but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4+-regulatory T (Treg) cell induction, and restrain CD8+ T cell effector function. Tumor colonization is accompanied by PHD protein-dependent induction of pulmonary Treg cells and suppression of IFN-g-dependent tumor clearance. T cell-intrinsic deletion or pharmacological inhibition of PHD proteins limits tumor colonization of the lung and improves the efficacy of adoptive cell transfer immunotherapy. Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis.
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| Overall design |
RNA expression was measured by RNA-Seq at day 4 following stimulation of naïve FACS-sorted CD4+ T cells with anti-CD3 and anti-CD28 antibodies in the presence of indicated doses of TGF-b. Gene expression was analysed separately in control Cd4Cre (WT) and Egln1fl/fl Egln2fl/fl Egln3fl/fl Cd4Cre (tKO) cells, or in cells treated with the pharmacological PHD inhibitor dimethyloxaloylglycine (DMOG) and control vehicle-treated cells.
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| Contributor(s) |
Clever D, Roychoudhuri R, Constantinides MG, Askenase MH, Sukumar M, Klebanoff CA, Eil RL, Hickman HD, Yu Z, Pan JH, Palmer DC, Phan AT, Goulding J, Gattinoni L, Goldrath AW, Belkaid Y, Restifo NP |
| Citation(s) |
27565342 |
| Submission date |
Aug 03, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Rahul Roychoudhuri |
| E-mail(s) |
rr257@cam.ac.uk
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| Organization name |
University of Cambridge
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| Department |
Department of Pathology
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| Lab |
Roychoudhuri Laboratory
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| Street address |
Tennis Court Road
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| City |
Cambridge |
| ZIP/Postal code |
CB2 1QP |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA336280 |
| SRA |
SRP080852 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE85131_Clever_et_al_PHD_proteins_2016_FPKM_Exp1.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE85131_Clever_et_al_PHD_proteins_2016_FPKM_Exp2.txt.gz |
566.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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