Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma

Q. Wang, Y. Lu, R. Li, Y. Jiang, Y. Zheng, J. Qian, E. Bi, C. Zheng, J. Hou, S. Wang, Q. Yi

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Our previous studies showed that macrophages (MΦs), especially myeloma-associated MΦs (MAMs), induce chemoresistance in human myeloma. Here we explored the potential of targeting MΦs, 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 MΦs and MAMs, and repolarized MAMs towards M1-like MΦs 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 MΦs in myeloma-bearing MMDTR 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 MΦs. Thus, this study provides the first direct in vivo evidence that MΦs 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 antimyeloma immune responses in patients.

Original languageEnglish (US)
Pages (from-to)176-183
Number of pages8
JournalLeukemia
Volume32
Issue number1
DOIs
StatePublished - Jan 2018

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma'. Together they form a unique fingerprint.

Cite this