Evidence map›Paper›PMID 24216477›Full record

ArticleThe Journal of clinical investigation2013

Interferon-dependent IL-10 production by Tregs limits tumor Th17 inflammation.

C Andrew Stewart, Hannah Metheny, Noriho Iida, Loretta Smith, Miranda Hanson, Folkert Steinhagen, Robert M Leighty, Axel Roers, Christopher L Karp, Werner Müller and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 2 pooled it
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.

  1. Pooled it
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  13. Endogenous retroelements promote tolerance to dietary antigens.bioRxiv : the preprint server for biology · 2025
    Article
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  15. Article
  16. Cytokines in cancer.Cancer cell · 2025
    Review
  17. Review
  18. Review
  19. Article
  20. Article

44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

C Andrew Stewart
Hannah Metheny
Noriho Iida
Loretta Smith
Miranda Hanson
Folkert Steinhagen
Robert M Leighty
Axel Roers
Christopher L Karp
Werner Müller
Giorgio Trinchieri
University Hospital Bonn · DEUniversity Hospital Carl Gustav Carus · DEUniversity of Manchester · GB

Funding

Role of inflammation, innate resistance, and immunity in carcinogenesis.ZIABC010793 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TRINCHIERI, GIORGIO · 2009 to 2025
$16.8M
CCR NIH HHS HHSN261200800001CIntramural NIH HHSNCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

The capacity of IL-10 and Tregs in the inflammatory tumor microenvironment to impair anticancer Th1 immunity makes them attractive targets for cancer immunotherapy. IL-10 and Tregs also suppress Th17 activity, which is associated with poor prognosis in several cancers. However, previous studies have overlooked their potential contribution to the regulation of pathogenic cancer-associated inflammation. In this study, we investigated the origin and function of IL-10–producing cells in the tumor microenvironment using transplantable tumor models in mice. The majority of tumor-associated IL-10 was produced by an activated Treg population. IL-10 production by Tregs was required to restrain Th17-type inflammation. Accumulation of activated IL-10+ Tregs in the tumor required type I IFN signaling but not inflammatory signaling pathways that depend on TLR adapter protein MyD88 or IL-12 family cytokines. IL-10 production limited Th17 cell numbers in both spleen and tumor. However, type I IFN was required to limit Th17 cells specifically in the tumor microenvironment, reflecting selective control of tumor-associated Tregs by type I IFN. Thus, the interplay of type I IFN, Tregs, and IL-10 is required to negatively regulate Th17 inflammation in the tumor microenvironment. Therapeutic interference of this network could therefore have the undesirable consequence of promoting Th17 inflammation and cancer growth.

Indexed as

AnimalsCell Line, TumorHumansImmunotherapyInflammationInterferon Type IInterleukin-10Interleukin-17MiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptor, Interferon alpha-betaRNA, MessengerRNA, NeoplasmSignal TransductionIfnar1 protein, mouseIL10 protein, humanIL10 protein, mouseIl17a protein, mouseInterferon Type IInterleukin-10Interleukin-17Receptor, Interferon alpha-betaRNA, MessengerRNA, NeoplasmStat1 protein, mouseSTAT1 Transcription Factor

Identifiers

PMID24216477
PMCPMC3809773
OpenAlexW2091365300

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.