Multiple myeloma (MM) is a B-cell neoplasia characterized by the accumulation in the bone marrow of malignant plasma cells that produce monoclonal proteins and cause bone lesions, renal disease and immunodeficiency. Survival of MM cells in the bone marrow is supported by the bone barrow microenvironment, particularly macrophages (MØ). A recently published study (Gutiérrez-González et al. Blood, 2016) demonstrates that combining the GM-CSF cytokine plus the MIF (macrophage migration inhibitory factor) inhibitor 4-IPP (4-iodo-6-phenyl-pyrimidine) results in efficient reprogramming of the M2-like MØ (MM-associated macrophage, tumor permissive) to anti-tumoricidal M1-like MØ. Indeed, this combined treatment elicits a MØ-dependent therapeutic response in MM xenograft (human cells into immunodeficient mice) mouse models. Therefore, MØ reprogramming may constitute a novel and efficient therapeutic strategy to treat MM.
The work was led by Dr. Paloma Sánchez-Mateos from the Gregorio Marañón Hospital, in close collaboration with the groups of Drs. Joaquín Teixidó, Maria Angeles Garcia Pardo and Angel Corbí at the CIB, as well as with researchers from the CNIC, the 12 de Octubre and Puerta de Hierro hospitals in Madrid, and the University Hospital of Salamanca. The study was conducted as part of the Neoplasbim consortium and the Thematic Network for Cooperative Research in Cancer (RTICC), and funded by the Community of Madrid and Instituto de Salud Carlos III, respectively.