Open AccessInhibition of CSF-1R Supports T-Cell Mediated Melanoma Therapy
Author(s) -
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
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0104230
Subject(s) - immunotherapy , cd8 , melanoma , cancer research , immunosuppression , cytokine , cancer immunotherapy , angiogenesis , medicine , t cell , myeloid derived suppressor cell , myeloid , immunology , macrophage , granulocyte macrophage colony stimulating factor , chemistry , cancer , immune system , suppressor , in vitro , biochemistry
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.