کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2107809 | 1083702 | 2014 | 14 صفحه PDF | دانلود رایگان |
• Tumor-associated macrophages promote tumor progression
• Anti-CSF-1R antibody depletes tumor-associated macrophages in cancer patients
• CSF-1R inhibitor shows clinical activity in diffuse-type giant cell tumor patients
• CSF-1R signaling inhibition increases lymphocyte infiltration in cancer patients
SummaryMacrophage infiltration has been identified as an independent poor prognostic factor in several cancer types. The major survival factor for these macrophages is macrophage colony-stimulating factor 1 (CSF-1). We generated a monoclonal antibody (RG7155) that inhibits CSF-1 receptor (CSF-1R) activation. In vitro RG7155 treatment results in cell death of CSF-1-differentiated macrophages. In animal models, CSF-1R inhibition strongly reduces F4/80+ tumor-associated macrophages accompanied by an increase of the CD8+/CD4+ T cell ratio. Administration of RG7155 to patients led to striking reductions of CSF-1R+CD163+ macrophages in tumor tissues, which translated into clinical objective responses in diffuse-type giant cell tumor (Dt-GCT) patients.
Journal: - Volume 25, Issue 6, 16 June 2014, Pages 846–859