Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma.

ABSTRACT: Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs), induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4⁺ T-cell response. Similarly, genetically depleting MФs in myeloma-bearing MM^DTR mice retarded myeloma growth in vivo. Furthermore, the combination of CSF1

SUBMITTER: Wang Q 

PROVIDER: S-EPMC5927777 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature