Ma. Wright et al., STIMULATION OF IMMUNE SUPPRESSIVE CD34-MARROW BY LEWIS LUNG-CARCINOMATUMORS( CELLS FROM NORMAL BONE), Cancer immunology and immunotherapy, 46(5), 1998, pp. 253-260
Progressive growth of metastatic Lewis lung carcinoma (LLC-LN7) tumors
is associated with increased levels of bone-marrow-derived CD34+ cell
s having natural suppressor (NS) activity toward T cells. The present
studies determined whether tumor-derived products are responsible for
this induction of NS activity. Culturing normal bone marrow cells with
LLC-LN7-conditioned medium (LLC-CM) or with recombinant granulocyte/m
acrophage-colony-stimulating factor (GM-CSF) resulted in the appearanc
e of NS activity. The development of NS activity coincided with a prom
inent increase in the levels of CD34+ cells. That the CD34+ cells were
responsible for the NS activity of the bone marrow cultures containin
g LLC-CM was shown by the loss of NS activity when CD34+ cells were de
pleted. The stimulation of CD34+ NS cells by LLC-CM was attributed to
tumor production of GM-CSF, since neutralization of GM-CSF within the
LLC-CM reduced its capacity to increase CD34+ cell levels. Studies als
o showed that the induction of CD34+ NS cells by LLC-CM and GM-CSF cou
ld be overcome by including in the cultures an inducer of myeloid diff
erentiation, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. These r
esults demonstrate that the mechanism by which the LLC-LN7 tumors stim
ulate increased levels of CD34+ NS cells from normal bone marrow is by
their production of GM-CSF and that this can be blocked with the myel
oid differentiation inducer 1,25(OH)2D3.