Evidence map›Paper›PMID 38566518›Full record

ArticleClinical and translational medicine2024

Reciprocal crosstalk between Th17 and mesothelial cells promotes metastasis-associated adhesion of ovarian cancer cells.

Felix Neuhaus, Sonja Lieber, Veronika Shinkevich, Anna Mary Steitz, Hartmann Raifer, Kathrin Roth, Florian Finkernagel, Thomas Worzfeld, Andreas Burchert, Corinna Keber and 10 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

16 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 1 country.

Felix NeuhausInstitute of Systems Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.
Sonja LieberInstitute of Systems Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.
Veronika ShinkevichInstitute of Pharmacology, Philipps University, Marburg, Germany.
Anna Mary SteitzDepartment of Translational Oncology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.
Hartmann RaiferInstitute of Systems Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.
Kathrin RothCell Imaging Core Facility, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.
Florian FinkernagelBioinformatics Core Facility, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.
Thomas WorzfeldInstitute of Pharmacology, Philipps University, Marburg, Germany.
Andreas BurchertDepartment of Hematology, Oncology and Immunology, University Hospital Giessen and Marburg, Marburg, Germany.
Corinna KeberComprehensive Biomaterial Bank Marburg (CBBMR) and Institute of Pathology, Philipps University, Marburg, Germany.
Andrea NistGenomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University, Marburg, Germany.
Thorsten StieweGenomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University, Marburg, Germany.
Silke ReinartzDepartment of Translational Oncology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.ORCID 0009-0002-2851-193X
Vanessa M BeutgenInstitute of Translational Proteomics and Translational Proteomics Core Facility, Biochemical Pharmacological Centre, Philipps University, Marburg, Germany.ORCID 0000-0002-3354-2020
Johannes GraumannInstitute of Translational Proteomics and Translational Proteomics Core Facility, Biochemical Pharmacological Centre, Philipps University, Marburg, Germany.ORCID 0000-0002-3015-5850
Kim PauckTranslational Inflammation Research Division and Core Facility for Single Cell Multiomics, Philipps University, Marburg, Germany.
Holger GarnTranslational Inflammation Research Division and Core Facility for Single Cell Multiomics, Philipps University, Marburg, Germany.
Matthias GaidaInstitute of Pathology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany.ORCID 0000-0003-1499-7772
Rolf MüllerDepartment of Translational Oncology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.ORCID 0000-0003-3339-4248
Magdalena HuberInstitute of Systems Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany.
Philipps University of Marburg · DEGerman Center for Lung Research · DEJohannes Gutenberg University Mainz · DEUniversitätsklinikum Gießen und Marburg · DE

Funding

Deutsche Forschungsgemeinschaft GA1818/2-3Deutsche Forschungsgemeinschaft GRK2573Deutsche Forschungsgemeinschaft SFB1292-TP22Deutsche Forschungsgemeinschaft SFB1292-TPQ1
6 · The paper itself

Abstract

backgroundIL-17A and TNF synergistically promote inflammation and tumorigenesis. Their interplay and impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing on mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation.

methodsFlow-cytometry and immunohistochemistry experiments were employed to identify cellular sources of IL-17A and TNF. Changes in transcriptomes and secretomes were determined by bulk and single cell RNA sequencing as well as affinity proteomics. Functional consequences were investigated by microscopic analyses and tumor cell adhesion assays. Potential clinical implications were assessed by immunohistochemistry and survival analyses.

resultsWe identified Th17 cells as the main population of IL-17A- and TNF producers in ascites and detected their accumulation in early omental metastases. Both IL-17A and its receptor subunit IL-17RC were associated with short survival of OC patients, pointing to a role in clinical progression. IL-17A and TNF synergistically induced the reprogramming of mesothelial cells towards a pro-inflammatory mesenchymal phenotype, concomitantly with a loss of tight junctions and an impairment of mesothelial monolayer integrity, thereby promoting cancer cell adhesion. IL-17A and TNF synergistically induced the Th17-promoting cytokines IL-6 and IL-1β as well as the Th17-attracting chemokine CCL20 in mesothelial cells, indicating a reciprocal crosstalk that potentiates the tumor-promoting role of Th17 cells in OC.

conclusionsOur findings reveal a novel function for Th17 cells in the OC microenvironment, which entails the IL-17A/TNF-mediated induction of mesothelial-mesenchymal transition, disruption of mesothelial layer integrity and consequently promotion of OC cell adhesion. These effects are potentiated by a positive feedback loop between mesothelial and Th17 cells. Together with the observed clinical associations and accumulation of Th17 cells in omental micrometastases, our observations point to a potential role in early metastases formation and thus to new therapeutic options.

Indexed as

Ovarian NeoplasmsTh17 CellsCytokinesFemaleHumansInflammationInterleukin-17Tumor MicroenvironmentCytokinesInterleukin-17mesothelial cellsmetastasisovarian carcinomaTh17 cells

Identifiers

PMID38566518
PMCPMC10988119
OpenAlexW4393865246

What Socratic holds

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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 Socratic graph.