Evidence map›Paper›PMID 35666812›Full record

ArticleCancer research2022

IL6 and CCL18 Mediate Cross-talk between VHL-Deficient Kidney Cells and Macrophages during Development of Renal Cell Carcinoma.

Thi-Ngoc Nguyen, Hieu-Huy Nguyen-Tran, Chen-Yun Chen, Tien Hsu

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

Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Tumor-Induced PDPNInternational journal of molecular sciences · 2026
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  17. Targeting inerleukin-6 for renoprotection.Frontiers in immunology · 2024
    Review
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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 2 institutions in 1 country.

Thi-Ngoc NguyenDepartment of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan, Republic of China.
Hieu-Huy Nguyen-TranDepartment of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan, Republic of China.
Chen-Yun ChenDepartment of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan, Republic of China.
Tien HsuDepartment of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan, Republic of China.ORCID 0000-0003-2308-4297
China Medical University · TWNational Central University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Loss of the von Hippel-Lindau (VHL) tumor suppressor gene function accounts for 70% to 80% of all clear-cell renal cell carcinoma (ccRCC) cases, the most prevalent form of RCC. Accumulating evidence has indicated that ccRCC arises from sites of chronic inflammation, yet how ccRCC tumor cells interact with immune components of the microenvironment has not been fully elucidated. In this study, we used unbiased proteomic and genomic analyses on components of the tumor microenvironment under different conditions, identifying the molecular and cellular mechanisms that underlie the cross-talk between VHL-deficient kidney tubule cells and macrophages. In vitro and in a Vhlh conditional knockout mouse model, VHL-deficient noncancerous kidney epithelial cells, representing the early stage of ccRCC initiation, secreted IL6 that induced macrophage infiltration and polarization toward the protumorigenic M2 phenotype. Activated human macrophages secreted CCL18 and TGFβ1 to stimulate epithelial-to-mesenchymal transition (EMT) of the kidney tubule cells. Treatment with IL6-neutralizing antibody rescued inflammatory, proliferative, and EMT phenotypes of kidney epithelial cells in Vhlh conditional knockout mice. Furthermore, in a human ccRCC xenograft model, exogenous human primary or cultured macrophages significantly promoted primary tumor growth and metastasis in a CCL18-dependent manner. These findings identify specific factors involved in reciprocal cross-talk between tumor cells and immune components in the microenvironment, thus providing an avenue for early intervention in ccRCC. SIGNIFICANCE: The identification of VHL-deficient kidney tubule cell cross-talk with macrophages regulated by IL6 and CCL18 reveals potential targets for the prevention and treatment of ccRCC.

Indexed as

Carcinoma, Renal CellChemokines, CCInterleukin-6Kidney NeoplasmsAnimalsEpithelial CellsHumansKidneyMacrophagesMiceMice, KnockoutProteomicsTumor MicroenvironmentVon Hippel-Lindau Tumor Suppressor ProteinCCL18 protein, humanChemokines, CCIL6 protein, humanInterleukin-6VHL protein, humanVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID35666812
PMCPMC9662868
OpenAlexW4282943674

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.