Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

158 8 Interleukin-10 in Cancer Immunity
Tab. 8.2 Effects of IL-10 on immune cells
Cell population Suppression Induction Reference
Monocytes/
macrophages
TNF-a, IL-1, -8, -12 production;
antigen presentation
present the major target of IL-10. This is partly due to different levels of IL-10Ra expression
among the IL-10-responsive cell populations.
8.3.1
Effectson Myeloid Antigen-Presenting Cells(APC)
IL-1RA production;
phagocytosis
42±44, 47±51
DCs development; antigen presentation 39, 40, 141
T cells IL-2, -4, -5, IFN-g production;
proliferation
NK cells cytotoxic activity;
IFN-g,TNF-aproduction B cells proliferation; differentiation
58, 59, 142,
143
18, 69
70, 71
Neutrophils TNF-a, IL-1b, IL-8 production IL-1RA production 74, 75
Eosinophils TNF-a, GM-CSF, IL-8 production 77
Mast cells TNF-a, GM-CSF, NO production growth; histamine
liberation
78, 79, 144
Blood monocytes are very sensitive to the presence of IL-10. These cells are not a finally
differentiated population. After their 48 h residence in the circulation they emigrate
into the stromal tissues where they, depending on the micromilieu, develop
into more specialized cell populations, into either macrophages or type 1 dendritic
cells (DC1) [38]. IL-10 is able to prevent monocyte differentiation into DC1, which are
the most important APCs, especially for primary immune responses [39±41]. During
DC1 development the influence of IL-10 on these cells decreases. This is associated
with a decrease of cellular IL-10Ra expression (R. Sabat, unpublished). In contrast,
IL-10 supports monocyte maturation to macrophages and the sensitivity of macrophages
towards IL-10 is comparable to that of monocytes ([40] and R. Sabat, unpublished).
The functions of monocytes and macrophages which are regulated by IL-10
can be divided into three groups: (1) production of soluble immunomediators, (2)
antigen presentation and (3) phagocytosis. In general, IL-10 inhibits all those activities
that favor the inflammatory or specific cellular immune response and enhances
those activities that are associated with induction of tolerance in specific immunity as
well as with scavenger function. More concretely, IL-10 inhibits the production of
pro-inflammatory mediators by monocytes and macrophages, such as endotoxin- and
IFN-g-induced release of IL-1b, IL-6, IL-8, granulocyte colony stimulating factor
(CSF), granulocyte macrophage colony stimulating factor (GM-CSF) and tumor necrosis
factor (TNF)-a [42, 43]. In addition, it enhances the production of anti-inflammatory
mediators like IL-1RA and soluble TNF-a receptors [44±46]. Moreover, IL-10