Tumor-specific cytotoxic T cell generation and dendritic cell function are differentially regulated by interleukin 27 during development of anti-tumor immunity

Yukari Shinozaki, Sen Wang, Yoshiyuki Miyazaki, Kohji Miyazaki, Hisakata Yamada, Yasunobu Yoshikai, Hiromitsu Hara, Hiroki Yoshida

    Research output: Contribution to journalArticle

    46 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)1372-1378
    Number of pages7
    JournalInternational Journal of Cancer
    Volume124
    Issue number6
    DOIs
    Publication statusPublished - Mar 15 2009

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    Interleukin-27
    Dendritic Cells
    Immunity
    T-Lymphocytes
    Neoplasms
    Cytotoxic T-Lymphocytes
    Cytokines
    Antigens
    Perforin
    Experimental Melanomas
    Interleukin-12
    Growth

    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 journalArticle

    Shinozaki, Yukari ; Wang, Sen ; Miyazaki, Yoshiyuki ; Miyazaki, Kohji ; Yamada, Hisakata ; Yoshikai, Yasunobu ; Hara, Hiromitsu ; Yoshida, Hiroki. / Tumor-specific cytotoxic T cell generation and dendritic cell function are differentially regulated by interleukin 27 during development of anti-tumor immunity. In: International Journal of Cancer. 2009 ; Vol. 124, No. 6. pp. 1372-1378.
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    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.",
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    AU - Yamada, Hisakata

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    AU - Hara, Hiromitsu

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    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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