‫מחלקה המטולוגית‬
Department of Hematology
MD. ‫יאיר הרישנו‬
Yair Herishanu MD.
Nurse like cells- an in-vitro model for tumor associated macrophages
Nurse-like cells (NLC) is a model for tumor associated macrophages in chronic
lymphocytic leukemia (CLL). Based on this model, adherent cells appear, after 3 days of
culture of peripheral blood mononuclear cells (PBMC) obtained from CLL patients. After
a few more days of proliferation, these cells stop proliferating and by day 14 they appear
as large, round and occasionally bi-nucleated cells 1 , displaying a distinctive phenotype,
positive for vimentin, CD45, HLA-DR, CD33, CD14low ,CD68high , CD11b, CD80, CD86
and negative for CD106 and CD154 1, 2. Because CLL cells settle and arrange themselves
around these cells and are supported by them, they were initially termed “nurse like cells”
(NLC). These murse like cells were later also detected in-vivo, in the secondary lymphoid
tissues 2.
Nurse like cells appear to develop from CD14+ mononuclear cells and their
differentiation is dependent on cell to cell contact with CLL cells 2. In this respect it was
shown that cultured CD14+ depleted mononuclear cells from CLL patients cells do not
develop into nurse like cells 2. On the other hand, CD14+ cells obtained from normal
donors cocultured with selected B-CLL cells do differentiate into nurse like cells 2 while
normal B-cells do not induce differentiation of CD14+ cells into similar NLC 2.
Coculturing B-CLL cells with these nurse like cells protect them cells from spontaneous
and drug induced apoptosis
1, 3, 4
. NLC readily produce and secrete SDF-1 which can
stimulate B-CLL cells to show an improved survival1, 5while SDF -1 blocking antibodies
reduced the protective effects of nurse like cells on the B-CLL cell survival 1.
CXCL13 is also expressed and secreted from nurse like cells 6, induces B-CLL cell
migration 6 and prolongs their survival 5. CD31 and Plexin-B1 are also highly expressed
on the surface of nurse like cells
7
and either anti-CD31 or anti-Plexin-B1 blocking
antibodies reduce their stimulatory and prosurvival effect on cocultured B-CLL cells 7.
Nurse like cells have also been shown to express higher levels of BAFF and APRIL
compared to B-CLL cells 4and coculturing B-CLL cells with nurse like cells and BCMAFc (a decoy receptor that binds both BAFF and APRIL) partially abolishes the protective
effect of the nurse like cells on the viability of B-CLL cells 4.
References
1.
Burger, J. A. et al. Blood-derived nurse-like cells protect chronic lymphocytic
leukemia B cells from spontaneous apoptosis through stromal cell-derived factor1. Blood 96, 2655-63 (2000).
2.
Tsukada, N., Burger, J. A., Zvaifler, N. J. & Kipps, T. J. Distinctive features of
"nurselike" cells that differentiate in the context of chronic lymphocytic leukemia.
Blood 99, 1030-7 (2002).
3.
Burger, M. et al. Small peptide inhibitors of the CXCR4 chemokine receptor
(CD184) antagonize the activation, migration, and antiapoptotic responses of
CXCL12 in chronic lymphocytic leukemia B cells. Blood 106, 1824-30 (2005).
4.
Nishio, M. et al. Nurselike cells express BAFF and APRIL, which can promote
survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct
from that of SDF-1alpha. Blood 106, 1012-20 (2005).
5.
Ticchioni, M. et al. Homeostatic chemokines increase survival of B-chronic
lymphocytic leukemia cells through inactivation of transcription factor FOXO3a.
Oncogene (2007).
6.
Burkle, A. et al. Overexpression of the CXCR5 chemokine receptor, and its
ligand, CXCL13 in B cell chronic lymphocytic leukemia. Blood (2007).
7.
Deaglio, S. et al. CD38 and CD100 lead a network of surface receptors relaying
positive signals for B-CLL growth and survival. Blood 105, 3042-50 (2005).
For further information:
Yair Herishanu MD.
Department of Hematology
Tel Aviv Sourasky Medical Center, Tel Aviv University
6 Weizmann St, 64239, ISRAEL
Tel: 972-(3)-6974307
email1: yairh@tasmc.health.gov.il