Co-inhibition of colony stimulating factor-1 receptor and BRAF oncogene in mouse models of BRAF^V600E melanoma.

ABSTRACT: The presence of colony stimulating factor-1 (CSF1)/CSF1 receptor (CSF1R)-driven tumor-infiltrating macrophages and myeloid-derived suppressor cells (MDSCs) is shown to promote targeted therapy resistance. In this study, we demonstrate the superior effect of a combination of CSF1R inhibitor, PLX3397 and BRAF inhibitor, PLX4720, in suppressing primary and metastatic mouse BRAF^V600E melanoma. Using flow cytometry to assess SM1WT1 melanoma-infiltrating leukocytes immediately post therapy, we found that PLX3397 reduced the recruitment of CD11b⁺ Gr1^lo and CD11b⁺ Gr1^int M2-like macrophages, but this was accompanied by an accumulation of CD11b⁺ Gr1^hi cells. PDL1 expression on remaining myeloid cells potentially dampened t

SUBMITTER: Ngiow SF 

PROVIDER: S-EPMC4839378 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature