Abstract
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 antitnmor-effects using WSX-1 (IL-27 receptor α 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-speeiic 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1372-1378 |
| Number of pages | 7 |
| Journal | International Journal of Cancer |
| Volume | 124 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 15 2009 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Tumor-specific cytotoxic T cell generation and dendritic cell function are differentially regulated by interleukin 27 during development of anti-tumor immunity. / Shinozaki, Yukari; Wang, Sen; Miyazaki, Yoshiyuki; Miyazaki, Kohji; Yamada, Hisakata; Yoshikai, Yasunobu; Hara, Hiromitsu; Yoshida, Hiroki.
In: International Journal of Cancer, Vol. 124, No. 6, 15.03.2009, p. 1372-1378.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tumor-specific cytotoxic T cell generation and dendritic cell function are differentially regulated by interleukin 27 during development of anti-tumor immunity
AU - Shinozaki, Yukari
AU - Wang, Sen
AU - Miyazaki, Yoshiyuki
AU - Miyazaki, Kohji
AU - Yamada, Hisakata
AU - Yoshikai, Yasunobu
AU - Hara, Hiromitsu
AU - Yoshida, Hiroki
PY - 2009/3/15
Y1 - 2009/3/15
N2 - 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 antitnmor-effects using WSX-1 (IL-27 receptor α 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-speeiic 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.
AB - 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 antitnmor-effects using WSX-1 (IL-27 receptor α 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-speeiic 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.
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U2 - 10.1002/ijc.24107
DO - 10.1002/ijc.24107
M3 - Article
VL - 124
SP - 1372
EP - 1378
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 6
ER -