Evidence map›Paper›PMID 34719426›Full record

ArticleCancer cell2021

Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment.

Youmna Kfoury, Ninib Baryawno, Nicolas Severe, Shenglin Mei, Karin Gustafsson, Taghreed Hirz, Thomas Brouse, Elizabeth W Scadden, Anna A Igolkina, Konstantinos Kokkaliaris and 9 more

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

Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers.

0numbers the graph read from it
0cells of the map it votes in
197citing papers in PubMed
15.6field-weighted citation impact, top 1% 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

197 citing papers in PubMed, 255 citations in OpenAlex.

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137 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Youmna KfouryCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Ninib BaryawnoCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Childhood Cancer Research Unit, Department of Women's Health and Children's, Karolinska Institutet, Stockholm, Sweden. Electronic address: n.baryawno@ki.se.
Nicolas SevereCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Shenglin MeiDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Karin GustafssonCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Taghreed HirzCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Thomas BrouseCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Elizabeth W ScaddenCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Anna A IgolkinaSt. Petersburg Polytechnical University, St. Petersburg, Russia.
Konstantinos KokkaliarisCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Bryan D ChoiDepartment of Neurosurgery, Harvard Medical School, Boston, MA, USA.
Nikolas BarkasDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Mark A RandolphDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA, USA.
John H ShinDepartment of Neurosurgery, Harvard Medical School, Boston, MA, USA.
Philip J SaylorMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.
David T ScaddenCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
David B SykesCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Peter V KharchenkoHarvard Stem Cell Institute, Cambridge, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. Electronic address: peter_kharchenko@hms.harvard.edu.
as part of the Boston Bone Metastases Consortium
Harvard Stem Cell Institute · USHarvard University · USMassachusetts General Hospital · USPeter the Great St. Petersburg Polytechnic University · RU

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6M
Translational Imaging and Phenotyping CoreP30AR075042 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI Marie Demay · 2019 to 2026
$7.4M
Stromal Regulation of Bone MetastasisU54CA163191 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KALLURI, RAGHU · 2011 to 2015
$4.8M
Sequence-specific Hybridization Capture to Reveal the lncRNA Interactome in Prostate CancerR01CA193481 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI DAVID F. JARRARD, Lloyd M Smith · 2015 to 2026
$3.4M
Cell and Molecular Dynamics of Hematopoiesis In VivoR24DK103074 · NIDDK · HARVARD UNIVERSITY · PI SCADDEN, DAVID T · 2015 to 2018
$3.0M
Statistical methods for analysis of single-cell variabilityR01HL131768 · NHLBI · HARVARD MEDICAL SCHOOL · PI KHARCHENKO, PETER V · 2015 to 2019
$2.4M
NCI NIH HHS P30 CA006516NCI NIH HHS R01 CA193481NCI NIH HHS U54 CA163191NHLBI NIH HHS R01 HL131768NIAMS NIH HHS P30 AR075042NIDDK NIH HHS R24 DK103074
6 · The paper itself

Abstract

Bone metastases are devastating complications of cancer. They are particularly common in prostate cancer (PCa), represent incurable disease, and are refractory to immunotherapy. We seek to define distinct features of the bone marrow (BM) microenvironment by analyzing single cells from bone metastatic prostate tumors, involved BM, uninvolved BM, and BM from cancer-free, orthopedic patients, and healthy individuals. Metastatic PCa is associated with multifaceted immune distortion, specifically exhaustion of distinct T cell subsets, appearance of macrophages with states specific to PCa bone metastases. The chemokine CCL20 is notably overexpressed by myeloid cells, as is its cognate CCR6 receptor on T cells. Disruption of the CCL20-CCR6 axis in mice with syngeneic PCa bone metastases restores T cell reactivity and significantly prolongs animal survival. Comparative high-resolution analysis of PCa bone metastases shows a targeted approach for relieving local immunosuppression for therapeutic effect.

Indexed as

Up-RegulationAnimalsBone NeoplasmsCase-Control StudiesCell Line, TumorChemokine CCL20Gene Expression Regulation, NeoplasticHumansMacrophagesMaleMiceMyeloid CellsProstatic NeoplasmsReceptors, CCR6Single-Cell AnalysisT-LymphocytesCCL20 protein, humanCCR6 protein, humanChemokine CCL20Receptors, CCR6bone marrowbone metastasishumanmouse modelprostate cancer bone metastasissingle-cell landscapesingle-cell RNA sequencingT cell exhaustion

Identifiers

PMID34719426
PMCPMC8578470
OpenAlexW3206010422

What Socratic 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 Socratic graph.