IL-10 is assumed to be a major immunosuppressive factor produced by most B-cell
tumors. The immunosuppressive role of
tumor-derived
IL-10 was analyzed using the MHC class II-negative BALB/c
plasmacytoma ADJ-PC-5 as a model
tumor. Immune monitoring of
tumor-bearing mice was based on the measurement of
tumor burden,
tumor-specific CTL cytotoxicity and intracellular
cytokine staining using FACS. ADJ-PC-5
tumor progression in syngeneic recipients is associated with strong, concomitant,
tumor-specific CTL responses during early stages of
tumor progression which are sufficient to cause rejection of small s.c. autologous test
tumors. These initial CTL responses gradually decline during later
tumor stages. Blocking of
IL-10 in vivo did not abolish CTL suppression or retard
tumor growth. More strikingly, application of anti-IL-10
antibodies during early
tumor stages abrogated CTL induction and markedly accelerated
tumor growth. In contrast to anti-IL-10 treatment, application of
cyclo-oxygenase inhibitors to ADJ-PC-5
tumor-bearing mice led to enhanced
tumor-specific CTL responses throughout all stages of
tumor progression, paralleled by retarded
tumor growth and a significantly delayed onset of suppression. Both findings contradict a dominant immunosuppressive role of
IL-10 during B-cell
tumor progression.
Tumor-derived
IL-10 must therefore be considered an immunostimulating factor, which accounts for the high immunogenicity of B-cell
tumors, whereas
prostaglandins, which are not produced by the
tumor cells themselves, are the dominant immunosuppressors in this system.