| First Author | Wang Q | Year | 2018 |
| Journal | Leukemia | Volume | 32 |
| Issue | 1 | Pages | 176-183 |
| PubMed ID | 28626216 | Mgi Jnum | J:254211 |
| Mgi Id | MGI:6110621 | Doi | 10.1038/leu.2017.193 |
| Citation | Wang Q, et al. (2018) Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma. Leukemia 32(1):176-183 |
| abstractText | Our previous studies showed that macrophages (Mcapital EF, Cyrillics), especially myeloma-associated Mcapital EF, Cyrillics (MAMs), induce chemoresistance in human myeloma. Here we explored the potential of targeting Mcapital EF, Cyrillics, 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 Mcapital EF, Cyrillics and MAMs, and repolarized MAMs towards M1-like Mcapital EF, Cyrillics 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 Mcapital EF, Cyrillics in myeloma-bearing MM(DTR) mice retarded myeloma growth in vivo. Furthermore, the combination of CSF1R blockade and chemotherapy such as bortezomib or melphalan displayed an additive therapeutic efficacy against established myeloma. Finally, a fully human CSF1R blocking mAb, similar to its murine counterpart, was able to inhibit the differentiation, proliferation and survival of human Mcapital EF, Cyrillics. Thus, this study provides the first direct in vivo evidence that MPhis and MAMs are indeed important for myeloma development and progression. Our results also suggest that targeting MAMs by CSF1R blocking mAbs may be promising methods to (re)sensitize myeloma cells to chemotherapy and promote anti-myeloma immune responses in patients. |
