Evidence map›Paper›PMID 23418320›Full record

ArticleCancer research2013

CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer.

Jingying Xu, Jemima Escamilla, Stephen Mok, John David, Saul Priceman, Brian West, Gideon Bollag, William McBride, Lily Wu

Abstract read
In one paragraph

Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 359 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
359citing papers in PubMed, 2 pooled it
17.8field-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

359 citing papers in PubMed, 2 syntheses or guidelines pooled it, 558 citations in OpenAlex.

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  12. Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026
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299 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Jingying XuDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095-1735, USA.
Jemima Escamilla
Stephen Mok
John David
Saul Priceman
Brian West
Gideon Bollag
William McBride
Lily Wu
City of Hope · USBeckman Research InstitutePlexxikon (United States)City Of Hope National Medical Center · USUniversity of California, Los Angeles · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREEMAN, MICHAEL R · 2002 to 2023
$42.6M
UCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5M
Gene-Based Imaging and Therapy To Target Prostate CancerR01CA101904 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WU, LILY · 2003 to 2012
$2.9M
NCATS NIH HHS UL1 TR000124NCI NIH HHS P50 CA092131NCI NIH HHS R01 CA101904NCRR NIH HHS 1UL1RR033176NCRR NIH HHS UL1 RR033176
6 · The paper itself

Abstract

Radiotherapy is used to treat many types of cancer, but many treated patients relapse with local tumor recurrence. Tumor-infiltrating myeloid cells (TIM), including CD11b (ITGAM)(+)F4/80 (EMR1)+ tumor-associated macrophages (TAM), and CD11b(+)Gr-1 (LY6G)+ myeloid-derived suppressor cells (MDSC), respond to cancer-related stresses and play critical roles in promoting tumor angiogenesis, tissue remodeling, and immunosuppression. In this report, we used a prostate cancer model to investigate the effects of irradiation on TAMs and MDSCs in tumor-bearing animals. Unexpectedly, when primary tumor sites were irradiated, we observed a systemic increase of MDSCs in spleen, lung, lymph nodes, and peripheral blood. Cytokine analysis showed that the macrophage colony-stimulating factor CSF1 increased by two-fold in irradiated tumors. Enhanced macrophage migration induced by conditioned media from irradiated tumor cells was completely blocked by a selective inhibitor of CSF1R. These findings were confirmed in patients with prostate cancer, where serum levels of CSF1 increased after radiotherapy. Mechanistic investigations revealed the recruitment of the DNA damage-induced kinase ABL1 into cell nuclei where it bound the CSF1 gene promoter and enhanced CSF1 gene transcription. When added to radiotherapy, a selective inhibitor of CSF1R suppressed tumor growth more effectively than irradiation alone. Our results highlight the importance of CSF1/CSF1R signaling in the recruitment of TIMs that can limit the efficacy of radiotherapy. Furthermore, they suggest that CSF1 inhibitors should be evaluated in clinical trials in combination with radiotherapy as a strategy to improve outcomes.

Indexed as

Signal TransductionAnimalsCell LineCell Line, TumorCell MovementChromatinDNA DamageHumansImmunohistochemistryMacrophagesMaleMiceMice, Inbred C57BLMicroscopy, FluorescenceMyeloid CellsNeoplasm TransplantationChromatinReceptor, Macrophage Colony-Stimulating Factor

Identifiers

PMID23418320
PMCPMC4097014
OpenAlexW2105949723

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.