GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE85131 Query DataSets for GSE85131
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
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.
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.
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
Organization name University of Cambridge
Department Department of Pathology
Lab Roychoudhuri Laboratory
Street address Tennis Court Road
City Cambridge
ZIP/Postal code CB2 1QP
Country United Kingdom
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (18)
GSM2258145 WT1 0 ng/mL TGF-b
GSM2258146 WT1 0.2 ng/mL TGF-b
GSM2258147 WT1 2 ng/mL TGF-b
BioProject PRJNA336280
SRA SRP080852

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap