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Immunosuppression through constitutively activated NF-κB signalling in human ovarian cancer and its reversal by an NF-κB inhibitor
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Immunosuppression through constitutively activated NF-κB signalling in human ovarian cancer and its reversal by an NF-κB inhibitor
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Journal Article
Immunosuppression through constitutively activated NF-κB signalling in human ovarian cancer and its reversal by an NF-κB inhibitor
2014
Overview
Background:
Although T-cell immunity is thought to be involved in the prognosis of epithelial ovarian cancer (EOC) patients, immunosuppressive conditions hamper antitumour immune responses. Thus, their mechanisms and overcoming strategies need to be investigated.
Methods:
The role of NF-
κ
B in human EOC cells and macrophages was evaluated by
in vitro
production of immunosuppressive IL-6 and IL-8 by EOC cells and
in vivo
analysis of immune responses in nude mice implanted with human EOC cells using an NF-
κ
B inhibitor DHMEQ.
Results:
In EOC patients, increased plasma IL-6, IL-8, and arginase were observed. The NF-
κ
B inhibitor DHMEQ inhibited the production of IL-6 and IL-8 by EOC cell lines. Immunosuppression of human DCs and macrophages by culture supernatant of EOC cells was reversed with the pretreatment of DHMEQ. Administration of DHMEQ to nude mice implanted with human EOC resulted in the restoration of T-cell stimulatory activity of murine DCs along with the reduction of tumour accumulation and arginase expression of MDSCs. Nuclear factor-
κ
B inhibition in tumour-bearing mice also enhanced antitumour effects of transferred murine naive T cells.
Conclusions:
NF-
κ
B is involved in the immunosuppression induced by human EOC, and its inhibitor may restore antitumour immune responses, indicating that NF-
κ
B is an attractive target for EOC treatment.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ Carcinoma, Ovarian Epithelial
/ Culture Media, Conditioned - pharmacology
/ Cyclohexanones - pharmacology
/ Dendritic Cells - immunology
/ Female
/ Humans
/ Interleukin-6 - biosynthesis
/ Interleukin-8 - biosynthesis
/ Mice
/ Neoplasms, Glandular and Epithelial - immunology
/ Oncology
/ Ovarian Neoplasms - immunology
/ Signal Transduction - immunology
/ Transcription Factor RelA - antagonists & inhibitors
/ Transcription Factor RelA - genetics
