Open AccessSoluble factors derived from neuroblastoma cell lines suppress dendritic cell differentiation and activation
Author(s) -
Harada Kazuaki,
Ihara Fumie,
Takami Mariko,
Kamata Toshiko,
Mise Naoko,
Yoshizawa Hiroko,
Hishiki Tomoro,
Saito Takeshi,
Terui Keita,
Nakata Mitsuyuki,
Komatsu Shugo,
Ikeuchi Takayuki,
Nakayama Toshinori,
Yoshida Hideo,
Motohashi Shinichiro
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13933
Subject(s) - neuroblastoma , cell culture , tumor necrosis factor alpha , downregulation and upregulation , cytokine , dendritic cell , biology , cancer research , immunology , interferon , microbiology and biotechnology , immune system , chemistry , biochemistry , genetics , gene
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 CD 14 and upregulation of CD 1a, and dramatically decreased IL ‐12 and tumor necrosis factor ( TNF )‐α production from mature DC , while no effect of SH ‐ SY 5Y 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. CD 40 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.