Interleukin (IL-) 27 is a member of
IL-12 cytokine family with Th1-promoting and anti-inflammatory effects.
IL-27 has been shown to facilitate
tumor-specific cytotoxic T lymphocyte (CTL) induction against various
tumors. However,
IL-27 suppresses
cytokine production of lymphocytes and
antigen-presenting function of dendritic cells (DCs). To examine the in vivo role of
IL-27 in generation of anti-
tumor immunity, we examined IL-27-mediated antitumor-effects using WSX-1 (IL-27 receptor alpha chain)-deficient (WSX-1(-/-)) mice. In WSX-1(-/-) mice inoculated with
B16 melanoma cells,
tumor growth was higher than in wild-type (WT) mice. Accordingly,
tumor-specific CTL generation was lower in WSX-1(-/-) mice than in WT mice. CTL induction in WSX-1(-/-) mice was not restored by transfer of WT DCs pulsed with
TRP2 peptide, indicating that
IL-27 is directly required for generation of
tumor-specific CTLs. However, when transferred into
tumor-bearing mice, WSX-1(-/-) DCs pulsed with
TRP2 peptide was more potent than WT DCs in
tumor growth inhibition and generation of CTLs, indicating suppressive effects of
IL-27 on DC function. Finally, the combination of
WT CD8(+) T cells and KO DCs is more potent in generation of
antigen-specific CTLs than any other combinations. Expression of
perforin gene and percentages of
tumor-specific CD8(+) T cells were also the highest in the combination of WT CD8+ T cells and WSX-1(-/-) DCs. It was thus revealed that
IL-27 promotes CTL generation while suppressing DC function during generation of
tumor immunity. The combination of WT T cells and
IL-27 signal-defective DCs may have therapeutic potential against
tumors.