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 language | English |
|---|---|
| Pages (from-to) | 1748-1760 |
| Number of pages | 13 |
| Journal | Cell Reports |
| Volume | 14 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Feb 23 2016 |
Fingerprint
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease Progression. / Galletti, Giovanni; Scielzo, Cristina; Barbaglio, Federica; Rodriguez, Tania Véliz; Riba, Michela; Lazarevic, Dejan; Cittaro, Davide; Simonetti, Giorgia; Ranghetti, Pamela; Scarfò, Lydia; Ponzoni, Maurilio; Rocchi, Martina; Corti, Angelo; Anselmo, Achille; van Rooijen, Nico; Klein, Christian; Ries, Carola H.; Ghia, Paolo; De Palma, Michele; Caligaris-Cappio, Federico; Bertilaccio, Maria Teresa Sabrina.
In: Cell Reports, Vol. 14, No. 7, 23.02.2016, p. 1748-1760.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease Progression
AU - Galletti, Giovanni
AU - Scielzo, Cristina
AU - Barbaglio, Federica
AU - Rodriguez, Tania Véliz
AU - Riba, Michela
AU - Lazarevic, Dejan
AU - Cittaro, Davide
AU - Simonetti, Giorgia
AU - Ranghetti, Pamela
AU - Scarfò, Lydia
AU - Ponzoni, Maurilio
AU - Rocchi, Martina
AU - Corti, Angelo
AU - Anselmo, Achille
AU - van Rooijen, Nico
AU - Klein, Christian
AU - Ries, Carola H.
AU - Ghia, Paolo
AU - De Palma, Michele
AU - Caligaris-Cappio, Federico
AU - Bertilaccio, Maria Teresa Sabrina
PY - 2016/2/23
Y1 - 2016/2/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84959158011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959158011&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.01.042
DO - 10.1016/j.celrep.2016.01.042
M3 - Article
AN - SCOPUS:84959158011
VL - 14
SP - 1748
EP - 1760
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 7
ER -