Evidence map›Paper›PMID 29980788›Full record

ArticleOncogene2018

Histone deacetylase 6 regulates the immunosuppressive properties of cancer-associated fibroblasts in breast cancer through the STAT3-COX2-dependent pathway.

Ang Li, Ping Chen, Ye Leng, Jiuhong Kang

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 5% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.

  1. Role of STAT3 signaling pathway in breast cancer.Cell communication and signaling : CCS · 2020
    Pooled it
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Role of HDAC6 in carcinomas.Discover oncology · 2026
    Review
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  11. Review
  12. Review
  13. Article
  14. Article
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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

4 authors at 1 institution in 1 country.

Ang LiClinical and Translational Research Center of Shanghai First Maternity & Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, No. 1239 Siping Road, Shanghai, 200092, China.
Ping ChenClinical and Translational Research Center of Shanghai First Maternity & Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, No. 1239 Siping Road, Shanghai, 200092, China.
Ye LengClinical and Translational Research Center of Shanghai First Maternity & Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, No. 1239 Siping Road, Shanghai, 200092, China.
Jiuhong KangClinical and Translational Research Center of Shanghai First Maternity & Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, No. 1239 Siping Road, Shanghai, 200092, China. jhkang@tongji.edu.cn.
Shanghai First Maternity and Infant Hospital · CN

Funding

Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2016YFA0101300Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 16PJ1410200
6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) are important components in breast tumors and essential for tumor progression and metastasis. However, the role of epigenetic modification in driving the function of CAFs within breast tumors is only marginally known. Herein, we reported that histone deacetylase 6 (HDAC6), one of class II histone deacetylases, was frequently upregulated in the CAFs of breast tumor and promotes an immunosuppressive microenvironment. The genetic or pharmacologic disruption of HDAC6 in CAFs delays tumor growth, inhibits the tumor recruitment of myeloid-derived suppressor cells and regulatory T cells, alters the macrophage phenotype switch, and increases the CD8+ and CD4+ T-cell activation in vivo. Mechanistically, we identified prostaglandin E2/cyclooxygenase-2 (COX2) as a major target of HDAC6 in CAFs by regulating STAT3 activation. Overexpressing COX2 in HDAC6-knockdown CAFs can completely restore the immunosuppressive properties of the fibroblasts. Clinically, a positive correlation among the stromal expression levels of HDAC6, p-STAT3, and COX2 in human breast cancer was observed. High-stromal expression of HDAC6 was markedly associated with poor survival outcome. Overall, our findings indicated that fibroblastic HDAC6 was a vital epigenetic mediator involved in programming an immunosuppressive tumor microenvironment that dampens antitumor immunity. Thus, HDAC6 may be a good potential target to improve breast cancer immunotherapy.

Indexed as

Breast NeoplasmsAnimalsCancer-Associated FibroblastsCell Line, TumorCyclooxygenase 2FemaleHistone Deacetylase 6HumansMiceSignal TransductionSTAT3 Transcription FactorTumor EscapeTumor MicroenvironmentCyclooxygenase 2Histone Deacetylase 6STAT3 Transcription Factor

Identifiers

PMID29980788
OpenAlexW2821678286

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.