Evidence map›Paper›PMID 28754304›Full record

ArticleEBioMedicine2017

A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated Immunosuppression to Produce a Therapeutic Effect for Liver Cancer.

Wenbo Yao, Qian Ba, Xiaoguang Li, Huiliang Li, Shoude Zhang, Ya Yuan, Feng Wang, Xiaohua Duan, Jingquan Li, Weidong Zhang and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
5.9field-weighted citation impact, top 3% 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, 153 citations in OpenAlex.

  1. Trial
  2. Reprogramming macrophages to treat liver diseases.Hepatology (Baltimore, Md.) · 2026
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  10. Tumors in the setting of dupilumab use: A review of the literature.The World Allergy Organization journal · 2025
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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 5 institutions in 1 country.

Wenbo YaoKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Shanghai 200031, China.
Qian BaSchool of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Xiaoguang LiSchool of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Huiliang LiDepartment of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Shoude ZhangShanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Ya YuanKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Shanghai 200031, China.
Feng WangSchool of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
Xiaohua DuanSchool of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
Jingquan LiKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; University of Chinese Academy of Sciences, Shanghai 200031, China.
Weidong ZhangDepartment of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Hui WangKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China; University of Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: huiwang@sibs.ac.cn.
Shanghai Jiao Tong University · CNChinese Academy of Sciences · CNEast China University of Science and Technology · CNShanghaiTech University · CNSecond Military Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2 was demonstrated via calcium flux, the binding domain of CCR2 was identified in an extracellular loop by chimera binding assay, and in vivo antagonistic activity of 747 was confirmed through a thioglycollate-induced peritonitis model. In animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor-infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747 enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity, through elevating the numbers of intra-tumoral CD8+ T cells and increasing death of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have provided a new perspective on development of this antagonist for treatment of HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive microenvironment and potentiated the therapeutic effect of sorafenib, indicating that the combination of an immunomodulator with a chemotherapeutic drug could be a new approach for treating HCC.

Indexed as

AbiesAnimalsBinding SitesCarcinoma, HepatocellularCell Line, TumorCell ProliferationCell SurvivalDrug SynergismHep G2 CellsHumansImmunosuppression TherapyLiver NeoplasmsMacrophagesMiceNiacinamidePhenylurea CompoundsCCR2 protein, humanNiacinamidePhenylurea CompoundsPlant ExtractsReceptors, CCR2SorafenibCombination therapyExperimental therapeuticsImmunotherapyKaempferolPreclinical models

Identifiers

PMID28754304
PMCPMC5552238
OpenAlexW2735915489

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.