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

Giovanni Galletti, Cristina Scielzo, Federica Barbaglio, Tania Véliz Rodriguez, 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 Caligaris-CappioMaria Teresa Sabrina Bertilaccio

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish
Pages (from-to)1748-1760
Number of pages13
JournalCell Reports
Volume14
Issue number7
DOIs
Publication statusPublished - Feb 23 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Galletti, G., Scielzo, C., Barbaglio, F., Rodriguez, T. V., Riba, M., Lazarevic, D., Cittaro, D., Simonetti, G., Ranghetti, P., Scarfò, L., Ponzoni, M., Rocchi, M., Corti, A., Anselmo, A., van Rooijen, N., Klein, C., Ries, C. H., Ghia, P., De Palma, M., ... Bertilaccio, M. T. S. (2016). Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease Progression. Cell Reports, 14(7), 1748-1760. https://doi.org/10.1016/j.celrep.2016.01.042