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Tumor promoting immune suppressive myeloid derived suppressor cells in multiple myeloma microenvironment

Güllü Topal Görgün, Gregory Whitehill, Jennifer L. Anderson, Teru Hideshima, Craig Maguire, Jacob Laubach, Noopur Raje, Nikhil C. Munshi, Paul G. Richardson, Kenneth C. Anderson

Key points

  • MDSCs are increased in MM patients and have bidirectional interaction with tumor in MM microenvironment.

  • MM-MDSCs promotes MM growth and induce immune suppression; conversely, MM cells induce MDSC development.

Abstract

Myeloid derived suppressor cells (MDSCs) are a heterogeneous, immature myeloid cell population with the ability to suppress immune responses. MDSCs have been characterized in infections, inflammatory diseases, and solid tumors; however, their presence and role in the tumor promoting, immune suppressive microenvironment in hematologic malignancies remains unclear. Here we assessed the presence, frequency, and functional characteristics of MDSCs in patients with newly diagnosed, relapsed and relapsed/refractory multiple myeloma (MM), compared to healthy donors. Additionally, we evaluated the immunomodulatory effects of lenalidomide and bortezomib on MDSCs in MM. CD11b+CD14-HLA-DR-/lowCD33+CD15+ MDSCs were significantly increased in both PB and BM of patients with active MM compared to healthy donors. Furthermore, MDSCs induced MM growth, while suppressing T cell mediated immune responses. Conversely, MM cells induced development of MDSCs from healthy donor PBMCs, confirming a bidirectional interaction between MDSCs and MM cells and immune effector cells. Our results further suggest that MDSCs may be associated with activity of disease in MM. Importantly, our studies suggest that inhibition of the tumor promoting and immune suppressive functions of MDSCs in MM may represent a promising novel immune-based therapeutic strategy.

  • Submitted August 6, 2012.
  • Accepted January 2, 2013.