研究者業績

吉澤 比呂子

Yoshizawa Hiroko

基本情報

所属
千葉大学 医学部附属病院

J-GLOBAL ID
201901012308409647
researchmap会員ID
B000369149

論文

 1
  • Kazuaki Harada, Fumie Ihara, Mariko Takami, Toshiko Kamata, Naoko Mise, Hiroko Yoshizawa, Tomoro Hishiki, Takeshi Saito, Keita Terui, Mitsuyuki Nakata, Shugo Komatsu, Takayuki Ikeuchi, Toshinori Nakayama, Hideo Yoshida, Shinichiro Motohashi
    Cancer science 110(3) 888-902 2019年3月  査読有り
    Dendritic cells (DC) play a key role in the initiation of both antitumor immunity and immunological tolerance. It has been demonstrated that exposure to soluble factors produced by tumor cells modulates DC functions and induces tolerogenic DC differentiation. In this study, we investigated the effects of neuroblastoma cell line-derived soluble factors on DC differentiation. Monocytes isolated from healthy volunteers were incubated with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor in the presence of culture supernatants from neuroblastoma cell lines. The culture supernatants from neuroblastoma cell lines, such as NLF and GOTO, partially blocked both downregulation of CD14 and upregulation of CD1a, and dramatically decreased IL-12 and tumor necrosis factor (TNF)-α production from mature DC, while no effect of SH-SY5Y cell supernatant was noted. In addition, IL-6 and IL-10 production from monocytes was increased by the supernatants of NLF and GOTO cells at 24 hours after incubation. Furthermore, we evaluated DC functions through stimulation of invariant natural killer T (iNKT) cells. α-Galactosylceramide-pulsed DC co-cultured with supernatants of NLF cells were unable to sufficiently stimulate iNKT cells. The decreased ability of iNKT cells to produce interferon (IFN)-γ after stimulation with neuroblastoma cell line supernatant-cultured DC was reversed by addition of IL-12. CD40 expression and IL-12 production in NLF-sup-treated DC were increased by addition of exogenous IFN-γ. These results indicate that tolerogenic DC are induced in the neuroblastoma tumor microenvironment and attenuate the antitumor effects of iNKT cells. Interactions between iNKT cells and αGalCer-pulsed DC have the potential to restore the immunosuppression of tolerogenic DC through IFN-γ production.

MISC

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