Malignant cells may escape from the immune response in vivo because of a de
fective differentiation of professional antigen-presenting cells (APCs), Le
., dendritic cells (DCs). We recently reported that tumor cells release int
erleukin (LC)-6 and macrophage colony stimulating factor (M-CSF), which inh
ibit the differentiation of CD34(+) cells into DCs and promote their commit
ment toward monocytic lineage with a poor APC function. The results present
ed here show that both IL-4 and IL-13 reverse the inhibitory effects of ren
al cell carcinoma conditioned media (RCC CM) or IL-6+M-CSF on the phenotypi
c and functional differentiation of CD34(+) into DCs. IL-4 was found to act
through a rapid blockade of the expression of M-CSF and the IL-6 receptor-
transducing chain (gp130), along with a decrease of the secondary productio
n of M-CSF, thereby preventing the loss of granulocyte macrophage colony st
imulating factor (GM-CSF) receptor Lu chain expression on differentiating C
D34(+) cells. Consistent with these observations, the differentiation of DC
s from monocytes cultured with GM-CSF and IL-4 was also impaired by RCC Chi
, but the minimal inhibitory concentrations of RCC CM were 10-fold higher t
han for CD34(+) cells. In these conditions, monocytes cultured with GM-CSF
and IL-4 also exhibited profound phenotypic changes (CD14(+) CD32(+)CD86(+)
HLA-DR(+)CD115(low)CD23(low)CD1a(-)) and a poor APC function. These alterat
ions were overcome in a dose-dependent manner by IL-4 (5-500 IU/ml), althou
gh not beyond a 40% final concentration of RCC CM. The capacity of RCC CM t
o block DC differentiation from monocytes strongly correlated with IL-6 and
M-CSF concentrations in medium. Taken together, these results demonstrate
that IL-4 and IL-13 reverse the inhibitory effect of tumor cells on DC diff
erentiation.