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

3. How immunogenic are the tumor cells? What is the most relevant mechanism
for protection against the tumor ± the NK-cell mediated lysis or the specific immunity
(DC1, CD4 + and CD8 + T cells)?
Thus it is understandable that IL-10 enhances the growth of some tumors like certain
lymphomas (IL-10 enhances the proliferation of these cells, no relevance of neovascularization,
immune protection particularly given through specific immunity),
while inhibiting other tumor species (important role of neovascularization, protection
given by NK cells).
In addition, at least two further aspects are likely to be relevant for the final effect of
IL-10:
1. The concentration of the cytokine.
2. The time and duration of its presence.
8.6 Conclusions
The IL-10 concentration does not only seem to be relevant for the quantity but also
for quality of the effects. Based on our recent in vivo and in vitro observations we
speculate that low concentrations of IL-10 are efficient for negative effects on immune
cells, whereas higher concentrations are needed for stimulatory effects. As discussed
before, negative regulatory effects of IL-10 are only seen when applied early
in an immune response. Overall, we think that for the majority of tumors IL-10 contributes
to tumor escape from an immune response, especially in the beginning of
the disease.
Whatever the role of IL-10 on tumors might be, the question arises whether the
modulation of IL-10 levels will result in therapeutic effects. A decrease of IL-10
serum levels can be safely achieved by anti-IL-10 antibodies [135]. Reduction of IL-10
levels might only be useful in tumors where IL-10 acts as an autocrine growth factor.
For most of the patients submitted to the hospital it may not work as they are already
in a late stage of disease with reduced antitumor immunity. Additionally, regulatory
T cells might already be generated. On the other hand, depletion of IL-10 could increase
the inflammatory activity of monocytes and macrophages, resulting in further
dysregulation of the immune system (massive inflammation does inhibit specific
immunity).
The opposite treatment ± application of IL-10 ± has also been performed in healthy
volunteers and numerous, different patients [11, 60]. Application of IL-10 may be
useful in some tumors, especially at progressed stages. Specific immunity is already
inhibited, thus negative effects should not be expected. In contrast, IL-10 could increase
NK cell-mediated tumor lysis and inhibit angiogenesis. Importantly, proliferative
effects on the tumor need to be excluded before IL-10 application.
Ongoing trials will show whether theory will fit with nature.
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