Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: T cell oxygen-sensing proteins establish an immunologically tolerant metastatic niche      
keywords:
Transcriptome or Gene expression
ID:
PRJNA336280
description:
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.
accesstypes:
download
landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA336280
authentication:
none
authorization:
none
ID:
pmid:27565342
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • BBS/E/B/000C0409/Biotechnology and Biological Sciences Research Council/United Kingdom

  • R01 AI096852/AI/NIAID NIH HHS/United States

  • T32 GM007240/GM/NIGMS NIH HHS/United States

  • BB/N007794/1/Biotechnology and Biological Sciences Research Council/United Kingdom

  • BBS/E/B/000C0407/Biotechnology and Biological Sciences Research Council/United Kingdom

  • Z01 BC010763-03/NULL/Intramural NIH HHS/United States

  • Z01 BC010763-02/NULL/Intramural NIH HHS/United States

  • Wellcome Trust/United Kingdom

Feedback?

If you are having problems using our tools, or if you would just like to send us some feedback, please post your questions on GitHub.