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

that IL-10 may dominate over type 1 (IFN-g) and Type 2 (IL-4) cytokines [91, 92, 95±
98]. Whether IL-10 expression is accompanied by a quantitatively similar inflammatory
reaction (TNF-a and IL-1b) cannot be concluded from these studies. It should
be mentioned that the systemic deviation of the immune system towards a type 2
phenotype has been postulated in cancer patients [99]. However, to our mind IL-10 is
not just a classical type 2 cytokine, and the systemic cytokine phenotype in tumor patients
often does not match the classical type 2 phenotype.
8.4.3
IL-10 Presence: Local or Systemic?
The studies described above show good documentation of local IL-10 expression in
tumors. Upon tumor progression IL-10 can also be detected in the circulation. As
early as 1993 Favrot et al. investigated IL-10 serum levels using ELISA which detects
both viral and human IL-10 in patients with active non-Hodgkin's lymphoma (NHL)
and healthy volunteers. They described the detection of IL-10 in serum from about
50 % of these patients but none of the control blood donors. IL-10 was detectable
with a similar frequency in all subtypes of NHL and in all clinical stages, as well as
in both EBV-seropositive and EBV-seronegative patients [100]. One year later Papa's
group demonstrated similar results obtained in patients with aggressive NHL [101].
In the following years these observations were extended to Hodgkin's disease and
other lymphoma species, and due to improved sensitivity of ELISA systems it could
be shown that lymphoma patients had significantly higher serum levels of IL-10
than healthy volunteers [102±107].
Another study reported by Brocker et al. in 1995 shows that IL-10 is detectable especially
in serum from progressed melanoma patients [108]. In the following years, elevated
levels of serum IL-10 were also observed in patients with other solid tumors
compared to healthy subjects. Extensive data are particularly available from patients
with lung and gastrointestinal carcinoma [109±114].
8.4.4
Prognostic Value of Enhanced IL-10 Expression
8.4 IL-10 Expression in Cancer Patients
In 1993, Favrot et al. reported that IL-10 serum levels in patients with NHL were an
independent prognostic factor. In patients with intermediate or high-grade NHL the
presence of serum IL-10 correlated with a significantly shorter progression-free and
overall survival [100]. The detection of human and viral IL-10 seems to be more relevant
than only the human form (reviewed in [103]). A very interesting observation
could be demonstrated in patients with chronic lymphocytic leukemia. Even if high
IL-10 mRNA expression in leukemic cells from these patients was strongly associated
with non-progressive disease [87], high IL-10 serum levels correlated with elevated
b2-microglobulin and LDH, and, more importantly, with worse median and 3year
survival [107]. In patients with Hodgkin's disease elevated IL-10 serum levels
were also associated with decreased progression-free and overall survival, independently
of other established prognostic factors [104±106]. Similar observations could
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