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Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition

Overview of attention for article published in BMC Cancer, May 2015
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (51st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

Mentioned by

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4 tweeters

Citations

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28 Dimensions

Readers on

mendeley
48 Mendeley
Title
Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition
Published in
BMC Cancer, May 2015
DOI 10.1186/s12885-015-1377-8
Pubmed ID
Authors

Stephen Mok, Jennifer Tsoi, Richard C Koya, Siwen Hu-Lieskovan, Brian L West, Gideon Bollag, Thomas G Graeber, Antoni Ribas

Abstract

Malignant melanoma is an aggressive tumor type that often develops drug resistance to targeted therapeutics. The production of colony stimulating factor 1 (CSF-1) in tumors recruits myeloid cells such as M2-polarized macrophages and myeloid derived suppressor cells (MDSC), leading to an immune suppressive tumor milieu. We used the syngeneic mouse model of BRAF (V600E) -driven melanoma SM1, which secretes CSF-1, to evaluate the ability of the CSF-1 receptor (CSF-1R) inhibitor PLX3397 to improve the antitumor efficacy of the oncogenic BRAF inhibitor vemurafenib. Combined BRAF and CSF-1R inhibition resulted in superior antitumor responses compared with either therapy alone. In mice receiving PLX3397 treatment, a dramatic reduction of tumor-infiltrating myeloid cells (TIM) was observed. In this model, we could not detect a direct effect of TIMs or pro-survival cytokines produced by TIMs that could confer resistance to PLX4032 (vemurafenib). However, the macrophage inhibitory effects of PLX3397 treatment in combination with the paradoxical activation of wild type BRAF-expressing immune cells mediated by PLX4032 resulted in more tumor-infiltrating lymphocytes (TIL). Depletion of CD8+ T-cells abrogated the antitumor response to the combination therapy. Furthermore, TILs isolated from SM1 tumors treated with PLX3397 and PLX4032 displayed higher immune potentiating activity. The combination of BRAF-targeted therapy with CSF-1R blockade resulted in increased CD8 T-cell responses in the SM1 melanoma model, supporting the ongoing evaluation of this therapeutic combination in patients with BRAF (V600) mutant metastatic melanoma.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Korea, Republic of 1 2%
Unknown 47 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 29%
Researcher 14 29%
Student > Master 4 8%
Student > Doctoral Student 3 6%
Unspecified 3 6%
Other 10 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 20 42%
Medicine and Dentistry 12 25%
Biochemistry, Genetics and Molecular Biology 6 13%
Immunology and Microbiology 4 8%
Unspecified 3 6%
Other 3 6%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 February 2016.
All research outputs
#3,212,316
of 7,211,484 outputs
Outputs from BMC Cancer
#1,048
of 3,210 outputs
Outputs of similar age
#91,479
of 201,176 outputs
Outputs of similar age from BMC Cancer
#78
of 194 outputs
Altmetric has tracked 7,211,484 research outputs across all sources so far. This one has received more attention than most of these and is in the 53rd percentile.
So far Altmetric has tracked 3,210 research outputs from this source. They receive a mean Attention Score of 3.3. This one has gotten more attention than average, scoring higher than 63% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 201,176 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 194 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.