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

the specific cellular immunity. By alteration of DC development and of naive Th1
cells, a new immune response is particularly affected. The influence of IL-10 on an
established immune response might be associated with the generation of regulatory
cells. The overall specific humoral immune responses are only loosely affected by IL-
10. It positively influences different functions of B cells, but likewise induces apoptosis
of DC2 and inhibits Th2 cells [80]. Finally, it remains to be mentioned that IL-10
enhances the unspecific cellular immunity, especially by modulating NK cells as
well as special functions of monocytes and macrophages.
Considering the time course of an immune response, the capacity of IL-10 to interfere
appears to be as follows. By inhibiting the inflammation and the establishment
of specific cellular immunity, IL-10 regulates the beginning of a new immune response.
The ongoing immune reaction is rather insensitive towards IL-10. However,
when the immune response slows down the regulatory role of IL-10 becomes important
again: IL-10 induces the generation of regulatory T cells and helps the macrophages
to `clean up' the site of reaction. It should be noted that the phagocytosed material
is not presented by the macrophages certainly representing a mechanism to
prevent the generation of auto-reactive T cells.
8.4
IL-10 Expression in Cancer Patients
Regarding IL-10 in cancer patients, four aspects appear to be especially interesting:
(1) the cellular sources of IL-10 (is it produced by tumor or immune cells), (2) the selectivity
of IL-10 production (is it only one cytokine among many others produced
under these circumstances), (3) the level and the dimension of IL-10 presence (is it
locally or systemically distributed, is it temporary or continuously expressed) and (4)
the prognostic value of enhanced IL-10 expression.
8.4.1
Cellular Sourcesof IL-10 in Cancer Patients
8.4 IL-10 Expression in Cancer Patients
The cellular origin of IL-10 found in cancer patients might give hints for its pathophysiological
role. Theoretically, IL-10 can be produced by the tumor cells as well as by
immune cells that for example infiltrate the tumor. If the first is true it may point to a
tumor-favoring role of IL-10. Such tumor-promoting effects could be achieved either
in an autocrine (stimulation of malignant cell proliferation) or in a paracrine manner
via the suppression of the antitumor immune response. This would support the idea
of an IL-10 neutralization as a new therapeutic approach. If IL-10 is produced by immune
cells (e.g. tumor-infiltrating cells), at least two different scenarios are possible.
One possibility would be that these cells produce IL-10 as part of their antitumor activity,
suggesting a tumor suppressive property of IL-10, achieved for instance by direct
inhibition of tumor cell growth or the enhancement of the antitumor activity of
other immune cells (e.g. NK cells). In this case, a therapeutic application of IL-10
would be reasonable. Another possibility, however, is that IL-10 production by im-
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