Evidence map›Paper›PMID 38846083›Full record

ArticleOncoimmunology2024

HUNK as a key regulator of tumor-associated macrophages in triple negative breast cancer.

Nicole Ramos Solis, Anthony Cannon, Tinslee Dilday, Melissa Abt, Adrian L Oblak, Adam C Soloff, Mark H Kaplan, Elizabeth S Yeh

Abstract read
In one paragraph

Article in Oncoimmunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
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  3. Review
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  5. Review
  6. Review
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

8 authors.

Nicole Ramos SolisDepartment of Pharmacology and Toxicology, Indiana University School of Medicine Indianapolis, Indianapolis, IN, USA.
Anthony CannonDepartment of Microbiology and Immunology, Indiana University School of Medicine Indianapolis, Indianapolis, IN, USA.
Tinslee DildayDepartment of Pharmacology and Toxicology, Indiana University School of Medicine Indianapolis, Indianapolis, IN, USA.
Melissa AbtDepartment of Pharmacology and Toxicology, Indiana University School of Medicine Indianapolis, Indianapolis, IN, USA.
Adrian L OblakDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, Indianapolis, IN, USA.
Adam C SoloffDepartment of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Mark H KaplanDepartment of Microbiology and Immunology, Indiana University School of Medicine Indianapolis, Indianapolis, IN, USA.
Elizabeth S YehDepartment of Pharmacology and Toxicology, Indiana University School of Medicine Indianapolis, Indianapolis, IN, USA.

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
BASIC SCIENCE STUDIES ON GENE THERAPY OF BLOOD DISEASEST32HL007910 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Roland W. Herzog, Reuben Kapur · 1999 to 2026
$7.6M
Immunology and Infectious Diseases Training ProgramT32AI060519 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MARK H KAPLAN · 2004 to 2026
$6.0M
Overcoming Resistance in HER2-positive Breast CancerR01CA187305 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI YEH, ELIZABETH S · 2015 to 2019
$1.8M
Tumor cell -TAM Paracrine Signaling in Breast CancerR01CA269508 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI Elizabeth Yeh · 2023 to 2026
$1.8M
HUNK Regulation of IL-4R03CA245774 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI YEH, ELIZABETH S · 2020 to 2020
$159k
NCI NIH HHS P30 CA082709NCI NIH HHS R01 CA187305NCI NIH HHS R01 CA269508NCI NIH HHS R03 CA245774NHLBI NIH HHS T32 HL007910NIAID NIH HHS T32 AI060519
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC tumors are not sensitive to endocrine therapy, and standardized TNBC treatment regimens are lacking. TNBC is a more immunogenic subtype of breast cancer, making it more responsive to immunotherapy intervention. Tumor-associated macrophages (TAMs) constitute one of the most abundant immune cell populations in TNBC tumors and contribute to cancer metastasis. This study examines the role of the protein kinase HUNK in tumor immunity. Gene expression analysis using NanoString's nCounter PanCancer Immune Profiling panel identified that targeting HUNK is associated with changes in the IL-4/IL-4 R cytokine signaling pathway. Experimental analysis shows that HUNK kinase activity regulates IL-4 production in mammary tumor cells, and this regulation is dependent on STAT3. In addition, HUNK-dependent regulation of IL-4 secreted from tumor cells induces polarization of macrophages into an M2-like phenotype associated with TAMs. In return, IL-4 induces cancer metastasis and macrophages to produce epidermal growth factor. These findings delineate a paracrine signaling exchange between tumor cells and TAMs regulated by HUNK and dependent on IL-4/IL-4 R. This highlights the potential of HUNK as a target for reducing TNBC metastasis through modulation of the TAM population.

Indexed as

Protein Serine-Threonine KinasesTriple Negative Breast NeoplasmsAnimalsCell Line, TumorDisease Models, AnimalErbB ReceptorsFemaleHumansInterleukin-4MacrophagesMiceMice, Inbred BALB CNeoplasm MetastasisReceptors, Interleukin-4Signal TransductionSTAT6 Transcription FactorEGFR protein, humanErbB ReceptorsHunk protein, mouseInterleukin-4Protein Serine-Threonine KinasesReceptors, Interleukin-4STAT6 Transcription FactorBreast cancerHUNKIL-4tumor associated macrophage

Identifiers

PMID38846083
PMCPMC11155704

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Registered trials

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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.