Evidence map›Paper›PMID 30488530›Full record

ArticleThe Prostate2019

Tumor-infiltrating mesenchymal stem cells: Drivers of the immunosuppressive tumor microenvironment in prostate cancer?

Timothy E Krueger, Daniel L J Thorek, Alan K Meeker, John T Isaacs, W Nathaniel Brennen

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

Article in The Prostate, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 5 pooled it
4.7field-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

63 citing papers in PubMed, 5 syntheses or guidelines pooled it, 85 citations in OpenAlex.

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  11. International journal of molecular sciences · 2025
    Article
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3 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

5 authors at 2 institutions in 1 country.

Timothy E KruegerDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Daniel L J ThorekMallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri.
Alan K MeekerDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins University, Baltimore, Maryland.
John T IsaacsDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins University, Baltimore, Maryland.ORCID 0000-0002-3854-4658
W Nathaniel BrennenDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins University, Baltimore, Maryland.ORCID 0000-0001-9807-7433
Johns Hopkins University · USWashington University in St. Louis · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
Kallikrein-Targeted Alpha-Particle Therapy of Late-Stage Prostate CancerR01CA201035 · NCI · WASHINGTON UNIVERSITY · PI THOREK, DANIEL LYNDON JAFFE · 2017 to 2020
$1.4M
NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236NCI NIH HHS R01 CA201035NCI NIH HHS R01CA201035NIH HHS P30 CA006973NIH HHS P30 CA058236
6 · The paper itself

Abstract

backgroundProstate cancer is characterized by T-cell exclusion, which is consistent with their poor responses to immunotherapy. In addition, T-cells restricted to the adjacent stroma and benign areas are characterized by anergic and immunosuppressive phenotypes. In order for immunotherapies to produce robust anti-tumor responses in prostate cancer, this exclusion barrier and immunosuppressive microenvironment must first be overcome. We have previously identified mesenchymal stem cells (MSCs) in primary and metastatic human prostate cancer tissue.

methodsAn Opal Multiplex immunofluorescence assay based on CD73, CD90, and CD105 staining was used to identify triple-labeled MSCs in human prostate cancer tissue. T-cell suppression assays and flow cytometry were used to demonstrate the immunosuppressive potential of primary MSCs expanded from human bone marrow and prostate cancer tissue from independent donors.

resultsEndogenous MSCs were confirmed to be present at sites of human prostate cancer. These prostate cancer-infiltrating MSCs suppress T-cell proliferation in a dose-dependent manner similar to their bone marrow-derived counterparts. Also similar to bone marrow-derived MSCs, prostate cancer-infiltrating MSCs upregulate expression of PD-L1 and PD-L2 on their cell surface in the presence of IFNγ and TNFα.

conclusionProstate cancer-infiltrating MSCs suppress T-cell proliferation similar to canonical bone marrow-derived MSCs, which have well-documented immunosuppressive properties with numerous effects on both innate and adaptive immune system function. Thus, we hypothesize that selective depletion of MSCs infiltrating sites of prostate cancer should restore immunologic recognition and elimination of malignant cells via broad re-activation of cytotoxic pro-inflammatory pathways.

Indexed as

Cell CommunicationHumansImmune ToleranceLymphocyte ActivationMaleMesenchymal Stem CellsPC-3 CellsProstatic NeoplasmsT-LymphocytesTumor Microenvironmentimmunotherapymesenchymal stem cellMSCprostate cancerT-cell exclusion

Identifiers

PMID30488530
PMCPMC6549513
OpenAlexW2903392710

What OpenQuestion holds

Textmetadata
LicenceTDM
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.