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 language | English (US) |
|---|---|
| Pages (from-to) | 2112-2121 |
| Number of pages | 10 |
| Journal | Leukemia and Lymphoma |
| Volume | 54 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2013 |
| Externally published | Yes |
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Keywords
- Immunotherapeutic approaches
- Immunotherapy
- Monocyte and macrophage biology
- Monocytes
- Myeloma
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
Cite this
Macrophages in multiple myeloma : Emerging concepts and therapeutic implications. / Asimakopoulos, Fotis; Kim, Jaehyup; Denu, Ryan A.; Hope, Chelsea; Jensen, Jeffrey L.; Ollar, Samuel J.; Hebron, Ellen; Flanagan, Claire; Callander, Natalie; Hematti, Peiman.
In: Leukemia and Lymphoma, Vol. 54, No. 10, 01.10.2013, p. 2112-2121.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Macrophages in multiple myeloma
T2 - Emerging concepts and therapeutic implications
AU - Asimakopoulos, Fotis
AU - Kim, Jaehyup
AU - Denu, Ryan A.
AU - Hope, Chelsea
AU - Jensen, Jeffrey L.
AU - Ollar, Samuel J.
AU - Hebron, Ellen
AU - Flanagan, Claire
AU - Callander, Natalie
AU - Hematti, Peiman
PY - 2013/10/1
Y1 - 2013/10/1
N2 - 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.
AB - 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.
KW - Immunotherapeutic approaches
KW - Immunotherapy
KW - Monocyte and macrophage biology
KW - Monocytes
KW - Myeloma
UR - http://www.scopus.com/inward/record.url?scp=84884493350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884493350&partnerID=8YFLogxK
U2 - 10.3109/10428194.2013.778409
DO - 10.3109/10428194.2013.778409
M3 - Review article
C2 - 23432691
AN - SCOPUS:84884493350
VL - 54
SP - 2112
EP - 2121
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 10
ER -