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

162 8 Interleukin-10 in Cancer Immunity
mune cells reflects a normal inflammation-limiting negative feedback response, leading
to the very same fatal results as if the tumor produces IL-10 itself. There are a
number of scientific groups that have studied the question of IL-10 origin.
Diamantstein's group could demonstrate selective expression of IL-10 mRNA in tissues
of primary melanomas and melanoma metastases in comparison to normal
skin. Additionally, they showed that some (three of 13) melanoma cell lines strongly
expressed IL-10 mRNA and produced biologically active cytokine. In contrast, normal
melanocytes, keratinocytes and fibroblasts did not produce detectable IL-10 protein
levels [81]. Similar results were reported by Brocker et al. This group additionally
observed a higher frequency of IL-10 expression in metastases compared to primary
tumors [82]. Strieter's group described increased levels of IL-10 protein in tissue
homogenates of human bronchogenic carcinomas compared to normal lung tissues.
Staining of these tumors illustrated primary localization of IL-10 protein to cancer
cells. Additionally, IL-10 protein was present in supernatants of several unstimulated
human bronchogenic cell lines [83]. IL-10 protein was also detected in culture supernatants
from cell lines of cutaneous carcinomas (basal and squamous cell carcinomas)
by ELISA and in the respective primary tumors by immunohistology [84]. Numerous
scientific groups have described that cells from B, T and NK cell lymphomas
are able to produce biologically active IL-10 [85±90].
The first evidence of other cellular sources of IL-10 production other than tumor
cells was found by Kiessling's group. They showed selective expression of IL-10
mRNA in biopsies from epithelial ovarian carcinomas in contrast to normal ovaries
and ovarian tumor cell lines. Since these differences could not be explained by the
extent of T cell infiltration, they suspected another population of immune cells as
the source of IL-10 [91]. Three years afterwards, this group reported similar observations
in patients with kidney carcinoma. IL-10 mRNA expression was detected only
in tumor samples, not in renal cancer lines, peripheral blood mononuclear cells
(PBMC) and non-tumorous kidney tissues from the same patients [92]. An explanation
for this might be delivered by results presented by Blay et al. This group also detected
IL-10 in renal cell carcinoma samples, but not in the culture supernatant of
cell lines derived from these tumors. However, these cell lines or their supernatants
induced IL-10 production by autologous monocytes and PBMC [93]. Interestingly,
very recently a novel subset of monocytes has been identified in peritoneal exudates
from patients with ovarian cancer. These monocytes were characterized by production
of IL-10 and TGF-b, but not IL-12 and TNF-a. In addition, they expressed CD14,
but not HLA-DR, CD86 or CD80 [94].
These examples prove that in tumor patients` tumor cells as well as immune cells
may produce IL-10. Whether the IL-10 production by one of these populations dominates
may depend on the kind of tumor and the actual state of the immune system.
8.4.2
Selectivity of IL-10 Production
There are only a few studies that quantitatively investigated the expression of IL-10
in malignant tissues in comparison with other cytokines. These few studies suggest