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KAKEN_25462614seika.pdf
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Title |
Title |
卵巣癌における癌免疫逃避機構の解明及び効果的な免疫治療法の開発
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Kana |
ランソウガン ニ オケル ガン メンエキ トウヒ キコウ ノ カイメイ オヨビ コウカテキナ メンエキ チリョウホウ ノ カイハツ
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Ransogan ni okeru gan meneki tohi kiko no kaimei oyobi kokatekina meneki chiryoho no kaihatsu
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Investigating cancer-immunoescape mechanism and effective immunotherapy for ovarian cancer
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西尾, 浩
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ニシオ, ヒロシ
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Nishio, Hiroshi
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慶應義塾大学・医学部・特任助教
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Research team head
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科研費研究者番号 : 90445239
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岩田, 卓
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イワタ, タカシ
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Iwata, Takashi
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慶應義塾大学・医学部・専任講師
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Research team member
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科研費研究者番号 : 30296652
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谷口, 智憲
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ヤグチ, トモノリ
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Romanization |
Yaguchi, Tomonori
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Affiliation |
慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 40424163
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2016
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科学研究費補助金研究成果報告書
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2015
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Abstract |
担がん生体における免疫抑制的な環境が引き起こす腫瘍免疫逃避の個体差が免疫療法の効果を損なう因子の一つと考えられている。今回, ヒト卵巣明細胞がんで活性化がみられる転写因子HNF-1bが抑制性サイトカインや抑制細胞を産生・誘導することで, 樹状細胞やT細胞の機能を抑制していることが示された。一方, HNF-1bを抑制することで樹状細胞やT細胞の機能が回復し免疫抑制からの解除が可能であることが細胞株, 卵巣がんモデルマウスより明らかとなった。これらの知見により, 本転写因子の制御は免疫療法の効果を増強する新たなターゲットとなりうることが示された。
Cancer-induced immunosuppression is one of the major problems for development of cancer immunotherapies. A transcriptional factor HNF-1β preferentially activated in human ovarian clear cell cancer (OCCC) have been reported. We have investigated roles of HNF-1β in the immunosuppressive activity of human OCCC. HNF-1β knockdown and overexpression experiments revealed that HNF-1β induced immunosuppressive cytokine production. In vitro suppressive activities of human OCCC culture supernatants on dendritic cell were reduced by knockdown of HNF-1β in cancer cells. In the mice model, knockdown of HNF-1β in the cancer cells resulted in restoration of T cell stimulatory activity of murine splenic DC in spleens and tumors. Therefore, HNF-1β activation in human OCCC is an upstream event for induction of immunosuppression, and is an attractive target for restoring immunocompetence in OCCC patients.
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研究種目 : 基盤研究(C)(一般)
研究期間 : 2013~2015
課題番号 : 25462614
研究分野 : 産婦人科学
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