Macrophages in multiple myeloma: Emerging concepts and therapeutic implications

Fotis Asimakopoulos, Jaehyup Kim, Ryan A. Denu, Chelsea Hope, Jeffrey L. Jensen, Samuel J. Ollar, Ellen Hebron, Claire Flanagan, Natalie Callander, Peiman Hematti

Research output: Contribution to journalReview article

30 Scopus citations

Abstract

Multiple myeloma, a clonal plasma cell malignancy, has long provided a prototypic model to study regulatory interactions between malignant cells and their microenvironment. Myeloma-associated macrophages have historically received limited scrutiny, but recent work points to central and non-redundant roles in myeloma niche homeostasis. The evidence supports a paradigm of complex, dynamic and often mutable interactions between macrophages and other cellular constituents of the niche. We and others have shown that macrophages support myeloma cell growth, viability and drug resistance through both contact-mediated and non-contact-mediated mechanisms. These tumor-beneficial roles have evolved in opposition to, or in parallel with, intrinsic pro-inflammatory and tumoricidal properties. Thus, simple blockade of protective "don't eat me" signals on the surface of myeloma cells leads to macrophage-mediated myeloma cell killing. Macrophages also enhance the tumor-supportive role of mesenchymal stem/stromal cells (MSCs) in the niche: importantly, this interaction is bidirectional, producing a distinct state of macrophage polarization that we termed "MSC-educated macrophages." The intriguing pattern of cross-talk between macrophages, MSCs and tumor cells highlights the myeloma niche as a dynamic multi-cellular structure. Targeted reprogramming of these interactions harbors significant untapped therapeutic potential, particularly in the setting of minimal residual disease, the main obstacle toward a cure.

Original languageEnglish (US)
Pages (from-to)2112-2121
Number of pages10
JournalLeukemia and Lymphoma
Volume54
Issue number10
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

Keywords

  • Immunotherapeutic approaches
  • Immunotherapy
  • Monocyte and macrophage biology
  • Monocytes
  • Myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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  • Cite this

    Asimakopoulos, F., Kim, J., Denu, R. A., Hope, C., Jensen, J. L., Ollar, S. J., Hebron, E., Flanagan, C., Callander, N., & Hematti, P. (2013). Macrophages in multiple myeloma: Emerging concepts and therapeutic implications. Leukemia and Lymphoma, 54(10), 2112-2121. https://doi.org/10.3109/10428194.2013.778409