Evidence map›Paper›PMID 20145121›Full record

ArticleCancer research2010

Blockade of tumor necrosis factor alpha signaling in tumor-associated macrophages as a radiosensitizing strategy.

Yuru Meng, Michael A Beckett, Hua Liang, Helena J Mauceri, Nico van Rooijen, Kenneth S Cohen, Ralph R Weichselbaum

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
8.6field-weighted citation impact, top 2% 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

107 citing papers in PubMed, 175 citations in OpenAlex.

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47 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

7 authors at 2 institutions in 2 countries.

Yuru MengDepartment of Radiation and Cellular Oncology and Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois 60637, USA.
Michael A Beckett
Hua Liang
Helena J Mauceri
Nico van Rooijen
Kenneth S Cohen
Ralph R Weichselbaum
University of Chicago · USVrije Universiteit Amsterdam · NL

Funding

Mechanisms of Resistance to Radio Inducible Gene TherapyR01CA111423 · NCI · UNIVERSITY OF CHICAGO · PI WEICHSELBAUM, RALPH R · 2005 to 2009
$1.5M
Recruitment of bone marrow stem cells to tumorsK08HL071938 · NHLBI · UNIVERSITY OF CHICAGO · PI COHEN, KENNETH STUART · 2003 to 2007
$650k
NCI NIH HHS CA111423NCI NIH HHS R01 CA111423NHLBI NIH HHS K08 HL071938NHLBI NIH HHS K08HL071938
6 · The paper itself

Abstract

Most cancer patients receive radiotherapy during the course of their disease. Improvements in the therapeutic index have been based mainly on physical improvements in delivery, as radiosensitizer development to target tumor cells has yet to yield effective agents. Recent investigations have focused on the tumor stroma as a target for radiosensitization. Here, we report that depletion of tumor-associated macrophages (TAMvarphi) by systemic or local injection of the macrophage-depleting liposomal clodronate before radiotherapy can increase the antitumor effects of ionizing radiation (IR), either as a large single dose (20 Gy) or as a fractionated dose (2 Gy x 10). Coimplantation of tumor cells with bone marrow-derived macrophages (BMDMvarphi) increased tumor radioresistance. Studies using mice with germline deletions in tumor necrosis factor receptors 1 and 2 (TNFR1,2(-/-)) or TNFalpha (TNF(-/-)), or treatment of wild-type mice with a soluble TNF receptor fusion protein (Enbrel), revealed that radioresistance mediated by BMDMvarphi required intact TNFalpha signaling. Radiation exposure upregulated vascular endothelial growth factor (VEGF) in macrophages and VEGF-neutralizing antibodies enhanced the antitumor response to IR. Thus, the radioprotective effect of TNFalpha was mediated by TAM-produced VEGF. Our findings offer a mechanistic basis to target macrophage populations generally or TNFalpha-induced macrophage VEGF specifically as tractable strategies to improve the efficacy of radiotherapy.

Indexed as

AnimalsCell ProliferationClodronic AcidDrug Evaluation, PreclinicalEtanerceptImmunoglobulin GLiposomesMacrophagesMiceMice, Inbred C57BLMice, KnockoutNeoplasmsRadiation-Sensitizing AgentsRadiation ToleranceReceptors, Tumor Necrosis FactorSignal TransductionClodronic AcidEtanerceptImmunoglobulin GLiposomesRadiation-Sensitizing AgentsReceptors, Tumor Necrosis FactorTumor Necrosis Factor-alphaVascular Endothelial Growth Factor A

Identifiers

PMID20145121
PMCPMC8849568
OpenAlexW2142449472

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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.