Lenalidomide is an immunomodulatory agent clinically active in chronic lymphocytic leukemia patients. The specific mechanism of action is still undefined, but includes modulation of the microenvironment. In chronic lymphocytic leukemia patients, nurse-like cells differentiate from CD14(+) mononuclear cells and protect chronic lymphocytic leukemia cells from apoptosis. Nurse-like cells resemble M2 macrophages with potent immunosuppressive functions. Here, we examined the effect of lenalidomide on the monocyte/macrophage population in chronic lymphocytic leukemia patients. We found that lenalidomide induces high actin polymerization on CD14(+) monocytes through activation of small GTPases, RhoA, Rac1 and Rap1 that correlated with increased adhesion and impaired monocyte migration in response to CCL2, CCL3 and CXCL12. We observed that lenalidomide increases the number of nurse-like cells that lost the ability to nurture chronic lymphocytic leukemia cells, acquired properties of phagocytosis and promoted T-cell proliferation. Gene expression signature, induced by lenalidomide in nurse-like cells, indicated a reduction of pivotal pro-survival signals for chronic lymphocytic leukemia, such as CCL2, IGF1, CXCL12, HGF1, and supported a modulation towards M1 phenotype with high IL2 and low IL10, IL8 and CD163. Our data provide new insights into the mechanism of action of lenalidomide that mediates a pro-inflammatory switch of nurse-like cells affecting the protective microenvironment generated by chronic lymphocytic leukemia into tissues.

Lenalidomide interferes with tumor-promoting properties of nurse-like cells in chronic lymphocytic leukemia / Fiorcari, Stefania; Martinelli, Silvia; Bulgarelli, Jenny; Audrito, V; Zucchini, Patrizia; Colaci, Elisabetta; Potenza, Leonardo; Narni, Franco; Luppi, Mario; Deaglio, S; Marasca, Roberto; Maffei, Rossana. - In: HAEMATOLOGICA. - ISSN 1592-8721. - 100:2(2015), pp. 253-262. [10.3324/haematol.2014.113217]

Lenalidomide interferes with tumor-promoting properties of nurse-like cells in chronic lymphocytic leukemia

FIORCARI, STEFANIA;MARTINELLI, Silvia;BULGARELLI, Jenny;ZUCCHINI, Patrizia;COLACI, ELISABETTA;POTENZA, Leonardo;NARNI, Franco;LUPPI, Mario;MARASCA, Roberto;MAFFEI, Rossana
2015

Abstract

Lenalidomide is an immunomodulatory agent clinically active in chronic lymphocytic leukemia patients. The specific mechanism of action is still undefined, but includes modulation of the microenvironment. In chronic lymphocytic leukemia patients, nurse-like cells differentiate from CD14(+) mononuclear cells and protect chronic lymphocytic leukemia cells from apoptosis. Nurse-like cells resemble M2 macrophages with potent immunosuppressive functions. Here, we examined the effect of lenalidomide on the monocyte/macrophage population in chronic lymphocytic leukemia patients. We found that lenalidomide induces high actin polymerization on CD14(+) monocytes through activation of small GTPases, RhoA, Rac1 and Rap1 that correlated with increased adhesion and impaired monocyte migration in response to CCL2, CCL3 and CXCL12. We observed that lenalidomide increases the number of nurse-like cells that lost the ability to nurture chronic lymphocytic leukemia cells, acquired properties of phagocytosis and promoted T-cell proliferation. Gene expression signature, induced by lenalidomide in nurse-like cells, indicated a reduction of pivotal pro-survival signals for chronic lymphocytic leukemia, such as CCL2, IGF1, CXCL12, HGF1, and supported a modulation towards M1 phenotype with high IL2 and low IL10, IL8 and CD163. Our data provide new insights into the mechanism of action of lenalidomide that mediates a pro-inflammatory switch of nurse-like cells affecting the protective microenvironment generated by chronic lymphocytic leukemia into tissues.
2015
14-nov-2014
100
2
253
262
Lenalidomide interferes with tumor-promoting properties of nurse-like cells in chronic lymphocytic leukemia / Fiorcari, Stefania; Martinelli, Silvia; Bulgarelli, Jenny; Audrito, V; Zucchini, Patrizia; Colaci, Elisabetta; Potenza, Leonardo; Narni, Franco; Luppi, Mario; Deaglio, S; Marasca, Roberto; Maffei, Rossana. - In: HAEMATOLOGICA. - ISSN 1592-8721. - 100:2(2015), pp. 253-262. [10.3324/haematol.2014.113217]
Fiorcari, Stefania; Martinelli, Silvia; Bulgarelli, Jenny; Audrito, V; Zucchini, Patrizia; Colaci, Elisabetta; Potenza, Leonardo; Narni, Franco; Luppi...espandi
File in questo prodotto:
File Dimensione Formato  
Fiorcari_Hematologica 2015 (NLC lenalidomide).pdf

Open access

Descrizione: pubblicazione scinetifica
Tipologia: Versione pubblicata dall'editore
Dimensione 586.08 kB
Formato Adobe PDF
586.08 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1081813
Citazioni
  • ???jsp.display-item.citation.pmc??? 22
  • Scopus 40
  • ???jsp.display-item.citation.isi??? 40
social impact