Inhibition of CSF-1R supports T-cell mediated melanoma therapy.
Tumor associated macrophages (TAM) can promote angiogenesis, invasiveness and immunosuppression. The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4128661?pdf=render |
id |
doaj-7debb9974bab4a178db9a4770e294bd7 |
---|---|
record_format |
Article |
spelling |
doaj-7debb9974bab4a178db9a4770e294bd72020-11-25T02:23:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10423010.1371/journal.pone.0104230Inhibition of CSF-1R supports T-cell mediated melanoma therapy.Marjolein SluijterTetje C van der SluisPieter A van der VeldenMieke VersluisBrian L WestSjoerd H van der BurgThorbald van HallTumor associated macrophages (TAM) can promote angiogenesis, invasiveness and immunosuppression. The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+) myeloid derived suppressor cells. Removal of intratumoral macrophages was remarkably efficient and a modest, but statistically significant, delay in melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly enhanced tumor control by immunotherapy using tumor-specific CD8 T cells. Elevated IFNγ production by T cells was observed in mice treated with the combination of PLX3397 and immunotherapy. These results support the combined use of CSF-1R inhibition with CD8 T cell immunotherapy, especially for macrophage-stimulating tumors.http://europepmc.org/articles/PMC4128661?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marjolein Sluijter Tetje C van der Sluis Pieter A van der Velden Mieke Versluis Brian L West Sjoerd H van der Burg Thorbald van Hall |
spellingShingle |
Marjolein Sluijter Tetje C van der Sluis Pieter A van der Velden Mieke Versluis Brian L West Sjoerd H van der Burg Thorbald van Hall Inhibition of CSF-1R supports T-cell mediated melanoma therapy. PLoS ONE |
author_facet |
Marjolein Sluijter Tetje C van der Sluis Pieter A van der Velden Mieke Versluis Brian L West Sjoerd H van der Burg Thorbald van Hall |
author_sort |
Marjolein Sluijter |
title |
Inhibition of CSF-1R supports T-cell mediated melanoma therapy. |
title_short |
Inhibition of CSF-1R supports T-cell mediated melanoma therapy. |
title_full |
Inhibition of CSF-1R supports T-cell mediated melanoma therapy. |
title_fullStr |
Inhibition of CSF-1R supports T-cell mediated melanoma therapy. |
title_full_unstemmed |
Inhibition of CSF-1R supports T-cell mediated melanoma therapy. |
title_sort |
inhibition of csf-1r supports t-cell mediated melanoma therapy. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Tumor associated macrophages (TAM) can promote angiogenesis, invasiveness and immunosuppression. The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+) myeloid derived suppressor cells. Removal of intratumoral macrophages was remarkably efficient and a modest, but statistically significant, delay in melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly enhanced tumor control by immunotherapy using tumor-specific CD8 T cells. Elevated IFNγ production by T cells was observed in mice treated with the combination of PLX3397 and immunotherapy. These results support the combined use of CSF-1R inhibition with CD8 T cell immunotherapy, especially for macrophage-stimulating tumors. |
url |
http://europepmc.org/articles/PMC4128661?pdf=render |
work_keys_str_mv |
AT marjoleinsluijter inhibitionofcsf1rsupportstcellmediatedmelanomatherapy AT tetjecvandersluis inhibitionofcsf1rsupportstcellmediatedmelanomatherapy AT pieteravandervelden inhibitionofcsf1rsupportstcellmediatedmelanomatherapy AT miekeversluis inhibitionofcsf1rsupportstcellmediatedmelanomatherapy AT brianlwest inhibitionofcsf1rsupportstcellmediatedmelanomatherapy AT sjoerdhvanderburg inhibitionofcsf1rsupportstcellmediatedmelanomatherapy AT thorbaldvanhall inhibitionofcsf1rsupportstcellmediatedmelanomatherapy |
_version_ |
1724859613768056832 |