RGD Reference Report - Human lung tumor FOXP3+ Tregs upregulate four "Treg-locking" transcription factors. - Rat Genome Database

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Human lung tumor FOXP3+ Tregs upregulate four "Treg-locking" transcription factors.

Authors: Akimova, Tatiana  Zhang, Tianyi  Negorev, Dmitri  Singhal, Sunil  Stadanlick, Jason  Rao, Abhishek  Annunziata, Michael  Levine, Matthew H  Beier, Ulf H  Diamond, Joshua M  Christie, Jason D  Albelda, Steven M  Eruslanov, Evgeniy B  Hancock, Wayne W 
Citation: Akimova T, etal., JCI Insight. 2017 Aug 17;2(16). pii: 94075. doi: 10.1172/jci.insight.94075. eCollection 2017 Aug 17.
RGD ID: 149735197
Pubmed: PMID:28814673   (View Abstract at PubMed)
PMCID: PMC5621877   (View Article at PubMed Central)
DOI: DOI:10.1172/jci.insight.94075   (Journal Full-text)

Experimental data indicate that FOXP3+ Tregs can markedly curtail host antitumor immune responses, but the properties of human intratumoral Tregs are still largely unknown, in part due to significant methodologic problems. We studied the phenotypic, functional, epigenetic, and transcriptional features of Tregs in 92 patients with non-small-cell lung cancer, comparing the features of Tregs within tumors versus corresponding blood, lung, and lymph node samples. Intratumoral Treg numbers and suppressive function were significantly increased compared with all other sites but did not display a distinctive phenotype by flow cytometry. However, by undertaking simultaneous evaluation of mRNA and protein expression at the single-cell level, we demonstrated that tumor Tregs have a phenotype characterized by upregulated expression of FOXP3 mRNA and protein as well as significantly increased expression of EOS, IRF4, SATB1, and GATA1 transcription factor mRNAs. Expression of these "Treg-locking" transcription factors was positively correlated with levels of FOXP3 mRNA, with highest correlations for EOS and SATB1. EOS had an additional, FOXP3 mRNA-independent, positive correlation with FOXP3 protein in tumor Tregs. Our study identifies distinctive features of intratumoral Tregs and suggests that targeting Treg-locking transcription factors, especially EOS, may be of clinical importance for antitumor Treg-based therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung cancer  IEP 149735197mRNA:increased expression:regulatory T cell:lung associated T cellRGD 
lung cancer  ISOGATA1 (Homo sapiens)149735197; 149735197mRNA:increased expression:regulatory T cell:lung associated T cellRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gata1  (GATA binding protein 1)

Genes (Mus musculus)
Gata1  (GATA binding protein 1)

Genes (Homo sapiens)
GATA1  (GATA binding protein 1)


Additional Information