Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities.

PubWeight™: 0.75‹?›

🔗 View Article (PMID 26423531)

Published in J Mol Med (Berl) on October 01, 2015

Authors

G Shay1, L Hazlehurst2, C C Lynch3

Author Affiliations

1: Tumor Biology Department, SRB-3, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Blvd, Tampa, FL, 33612, USA.
2: Department of Pharmaceutical Sciences and The Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, WV, 26506, USA.
3: Tumor Biology Department, SRB-3, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Blvd, Tampa, FL, 33612, USA. conor.lynch@moffitt.org.

Associated clinical trials:

A Phase 1 Study of Atezolizumab (an Engineered Anti-PDL1 Antibody) in Patients With Locally Advanced or Metastatic Solid Tumors | NCT01375842

Safety Study of Nivolumab by Itself or in Combination in Patients With Lymphoma or Multiple Myeloma | NCT01592370

A Phase 3 Study Comparing Oral Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma | NCT01564537

Kappa-CD28 T Lymphocytes, Chronic Lymphocytic Leukemia, B-cell Lymphoma or Multiple Myeloma, CHARKALL (CHARKALL) | NCT00881920

Blockade of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation | NCT01067287

A Study to Assess BHQ880 in Combination With Zoledronic Acid in Relapsed or Refractory Myeloma Patients | NCT00741377

IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma | NCT01850524

Ipilimumab or Nivolumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplant | NCT01822509

Treatment of Chemotherapy Refractory Multiple Myeloma by CART-138 (CART-138) | NCT01886976

A Phase I Open Label Study of the Safety and Tolerability of Elotuzumab (BMS-901608) Administered in Combination With Either Lirilumab (BMS-986015) or Urelumab (BMS-663513) in Subjects With Multiple Myeloma | NCT02252263

Lenalidomide and Pidilizumab in Treating Patients With Relapsed or Refractory Multiple Myeloma | NCT02077959

Study of T Cells Targeting B-Cell Maturation Antigen for Previously Treated Multiple Myeloma | NCT02215967

A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma | NCT02076009

IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic SCT | NCT01885897

Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer | NCT00060372

A Study of Pembrolizumab (MK-3475) in Combination With Standard of Care Treatments in Participants With Multiple Myeloma (MK-3475-023/KEYNOTE-023) | NCT02036502

QUILT-3.005: A Study of ALT-803 in Patients With Relapsed or Refractory Multiple Myeloma | NCT02099539

A Study of Siltuximab (Anti- IL 6 Monoclonal Antibody) in Patients With High-risk Smoldering Multiple Myeloma | NCT01484275

Expanded Natural Killer (NK) Cells for Multiple Myeloma Study | NCT01040026

1454GCC: Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma | NCT02289222

Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of GSK2857916 | NCT02064387

Phase 1/2a Study of Cancer Vaccine to Treat Smoldering Multiple Myeloma | NCT01718899

A Safety and Efficacy Study of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma | NCT01464034

Study of BHQ880 in Patients With High Risk Smoldering Multiple Myeloma | NCT01302886

Carfilzomib Plus Panobinostat in Relapsed/Refractory Multiple Myeloma (MM) | NCT01301807

Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma | NCT01668719

Study in Patients With Untreated Multiple Myeloma and Renal Insufficiency | NCT01337752

Bortezomib or Carfilzomib With Lenalidomide and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma | NCT01863550

Study of the Combination of Panobinostat & Carfilzomib in Patients With Relapsed &/or Refractory Multiple Myeloma | NCT01549431

Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma | NCT01881789

Autologous Stem Cell Transplant With Pomalidomide (CC-4047®) Maintenance Versus Continuous Clarithromycin/ Pomalidomide / Dexamethasone Salvage Therapy in Relapsed or Refractory Multiple Myeloma | NCT01745588

A Study of Oprozomib, Melphalan, and Prednisone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma | NCT02072863

Dinaciclib, Bortezomib, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma | NCT01711528

Carfilzomib, Lenalidomide, and Dexamethasone Before and After Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma | NCT01816971

"Monoclonal Antibodies for Treatment of Multiple Myeloma. Emphasis on the CD38 Antibody Daratumumab " (DARA) | NCT02419118

Dasatinib for Modulating Immune System After Autologous Stem Cell Transplants for Multiple Myeloma, Non-Hodgkin, or Hodgkin Lymphoma | NCT01609816

Dasatinib for Immune Modulation After Donor Stem Cell Transplant for Hematologic Malignancies | NCT01643603

Role of Osteocytes in Myeloma Bone Disease | NCT02212262

Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Relapsed or Refractory Multiple Myeloma | NCT01989598

UARK 2014-08 A Phase II Open-Label, Multiple-Dose, Single Agent Study to Evaluate the Overall Response Rate of Orally Administered Trametinib | NCT02140840

Articles cited by this

(truncated to the top 100)

The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol (2004) 19.38

Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A (2002) 12.39

Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol (2012) 12.19

Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood (2002) 9.40

Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature (1999) 8.23

Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell (2004) 7.61

Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol (2011) 6.16

The metastatic niche: adapting the foreign soil. Nat Rev Cancer (2009) 5.28

Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood (2001) 4.76

Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer (2012) 4.29

Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med (2006) 4.20

Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood (1999) 4.13

A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood (2005) 3.85

The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res (2008) 3.50

Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest (1999) 3.30

Synergistic control of cell adhesion by integrins and syndecans. Nat Rev Mol Cell Biol (2007) 3.21

Differential macrophage programming in the tumor microenvironment. Trends Immunol (2012) 3.18

History of myeloid-derived suppressor cells. Nat Rev Cancer (2013) 3.14

Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. Ann Oncol (2009) 3.08

Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol (1998) 2.96

Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol (2010) 2.85

The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol (2011) 2.83

Receptor activator of nuclear factor-kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo. Cancer Res (2003) 2.73

Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood (2007) 2.67

Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood (2009) 2.61

The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood (2010) 2.41

BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest (2013) 2.34

Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res (2004) 2.28

Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol (2011) 2.27

Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci U S A (2001) 2.27

Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. Crit Rev Eukaryot Gene Expr (2009) 2.26

Inhibitory effects of osteoblasts and increased bone formation on myeloma in novel culture systems and a myelomatous mouse model. Haematologica (2006) 2.11

The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene (2001) 2.04

The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacol (2011) 2.03

Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood (1993) 2.02

A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res (2013) 2.02

Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood (2001) 1.93

In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma. Blood (2006) 1.92

Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood (2002) 1.92

Host-derived adiponectin is tumor-suppressive and a novel therapeutic target for multiple myeloma and the associated bone disease. Blood (2011) 1.88

Enhancement of clonogenicity of human multiple myeloma by dendritic cells. J Exp Med (2006) 1.87

Cancer associated fibroblasts (CAFs) in tumor microenvironment. Front Biosci (Landmark Ed) (2010) 1.87

Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta (2013) 1.85

Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival. J Bone Miner Res (2003) 1.82

Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion. Blood (2004) 1.78

Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. Br J Haematol (2002) 1.74

Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer (2013) 1.74

Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell (2009) 1.73

Dysfunctional T regulatory cells in multiple myeloma. Blood (2005) 1.72

Bone marrow stromal cells protect myeloma cells from bortezomib induced apoptosis by suppressing microRNA-15a expression. Leuk Lymphoma (2011) 1.70

Myeloid-derived suppressor cell heterogeneity in human cancers. Ann N Y Acad Sci (2014) 1.69

Interleukin-6 and the network of several cytokines in multiple myeloma: an overview of clinical and experimental data. Cytokine (2001) 1.67

Mesenchymal stem cell abnormalities in patients with multiple myeloma. Leuk Lymphoma (2007) 1.66

Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10. Blood (2001) 1.63

Bone remodelling at a glance. J Cell Sci (2011) 1.62

Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood (2001) 1.60

Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity. Blood (2000) 1.59

Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis. Blood (2009) 1.58

Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma. Blood (2007) 1.55

Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica (2012) 1.53

CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia (2013) 1.52

The pathogenesis of the bone disease of multiple myeloma. Bone (2008) 1.51

PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother (2011) 1.47

Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo. J Bone Miner Res (2010) 1.39

Myeloma as a model for the process of metastasis: implications for therapy. Blood (2012) 1.36

Multiple myeloma: biology of the disease. Blood Rev (2010) 1.35

The role of the bone marrow microenvironment in the pathophysiology of myeloma and its significance in the development of more effective therapies. Hematol Oncol Clin North Am (2007) 1.26

From molds and macrophages to mevalonate: a decade of progress in understanding the molecular mode of action of bisphosphonates. Calcif Tissue Int (2004) 1.26

Dendritic cells control B cell growth and differentiation. Curr Dir Autoimmun (2005) 1.26

Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+myeloid-derived suppressor cells. PLoS One (2012) 1.25

Tumour-associated macrophages and cancer. Curr Opin Pharmacol (2013) 1.20

Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow. J Immunol (2013) 1.20

Immunosuppressive effects of multiple myeloma are overcome by PD-L1 blockade. Biol Blood Marrow Transplant (2011) 1.19

Role of decorin in the antimyeloma effects of osteoblasts. Blood (2008) 1.19

Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma. Br J Haematol (2001) 1.19

Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma. Oncogene (2007) 1.18

Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg/Th17 balance. Blood Cancer J (2013) 1.17

Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma. Clin Cancer Res (2003) 1.14

Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. Blood (2014) 1.13

Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership? J Pathol (2007) 1.12

Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells. Br J Haematol (2012) 1.12

Tgf-Beta inhibition restores terminal osteoblast differentiation to suppress myeloma growth. PLoS One (2010) 1.11

Effect of osteoclast activating factor from human leukocytes on bone metabolism. J Clin Invest (1975) 1.11

Lenalidomide enhances anti-myeloma cellular immunity. Cancer Immunol Immunother (2012) 1.10

Isolation and characterization of B cell differentiation factor (BCDF) secreted from a human B lymphoblastoid cell line. J Immunol (1984) 1.10

Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget (2013) 1.10

Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop. Blood (1996) 1.10

Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease. Blood (2001) 1.10

Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma. Hematol Oncol Clin North Am (1997) 1.09

Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood (2010) 1.09

Plasma cell differentiation and multiple myeloma. Curr Opin Immunol (2004) 1.08

Programmed death receptor-1/programmed death receptor ligand-1 blockade after transient lymphodepletion to treat myeloma. J Immunol (2013) 1.07

The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterisation of immune status in multiple myeloma. Br J Cancer (2012) 1.07

Multiple myeloma mesenchymal stem cells: characterization, origin, and tumor-promoting effects. Clin Cancer Res (2011) 1.06

Therapeutic effects of intrabone and systemic mesenchymal stem cell cytotherapy on myeloma bone disease and tumor growth. J Bone Miner Res (2012) 1.03

Smoldering multiple myeloma. Blood (2015) 1.03

Multiple myeloma induces the immunosuppressive capacity of distinct myeloid-derived suppressor cell subpopulations in the bone marrow. Leukemia (2012) 1.02

Regulatory T cells: major players in the tumor microenvironment. Curr Pharm Des (2009) 1.02

The treatment of relapsed and refractory multiple myeloma. Hematology Am Soc Hematol Educ Program (2007) 1.02

Myeloid cell diversification and complexity: an old concept with new turns in oncology. Cancer Metastasis Rev (2011) 1.01