Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease Progression

• DOI: 10.1016/j.celrep.2016.01.042
• Publication Date: 2016-02-13T17:57:27Z
• Authors: Giovanni Galletti; Cristina Scielzo; Federica Barbaglio; Tania Véliz Rodri...; Michela Riba; Dejan Lazarevic; Davide Cittaro; Giorgia Simonetti; Pamela Ranghetti; Lydia Scarfò; Maurilio Ponzoni; Martina Rocchi; Angelo Corti; Achille Anselmo; Nico van Rooijen; Christian Klein; Carola H. Ries; Paolo Ghia; Michele De Palma; Federico Caligari...; Maria Teresa Sabr...
• Keywords: 0301 basic medicine; Macrophage; Primary Cell Culture; Apoptosis; Mice, Transgenic; Cell Communication; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; B-Lymphocytes; Leukemia; Gene Expression Regulation, Leukemic; Macrophages; Antibodies, Monoclonal; CSF1R; Leukemia, Lymphocytic, Chronic, B-Cell; Survival Analysis; 3. Good health; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Liposomes; Disease Progression; Animals; Antibodies, Monoclonal; Apoptosis; B-Lymphocytes; Cell Communication; Cell Line, Tumor; Clodronic Acid; Disease Progression; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Liposomes; Macrophages; Mice; Mice, Transgenic; Neoplasm Transplantation; Primary Cell Culture; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Signal Transduction; Survival Analysis; Transplantation, Heterologous; Tumor Microenvironment; Gene Expression Regulation, Leukemic; Clodronic Acid; Neoplasm Transplantation; Signal Transduction

The role of monocytes/macrophages in the development and progression chronic lymphocytic leukemia (CLL) is poorly understood. Transcriptomic analyses show that leukemic cells cross talk during CLL progression. Macrophage depletion impairs engraftment, drastically reduces growth, favorably impacts mouse survival. Targeting macrophages by either CSF1R signaling blockade or clodrolip-mediated cell killing has marked inhibitory effects on established also. induces death mainly via TNF pathway reprograms tumor microenvironment toward an antitumoral phenotype. inhibition load, especially bone marrow, increases circulating CD20+ cells. Accordingly, co-targeting TAMs CD20-expressing provides a survival benefit mice. These results establish important suggest therapeutic strategies based interfering with leukemia-macrophage interactions.