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KAKEN_25670506seika.pdf
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悪性黒色腫の免疫抑制病態に関与するシグナル系の体系的解明と臨床応用
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アクセイ コクショクシュ ノ メンエキ ヨクセイ ビョウタイ ニ カンヨスル シグナルケイ ノ タイケイテキ カイメイ ト リンショウ オウヨウ
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Akusei kokushokushu no meneki yokusei byotai ni kanyosuru shigunarukei no taikeiteki kaimei to rinsho oyo
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Systematic analysis of cellular signaling involved in the melanoma induced immunosuppression
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河上, 裕
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カワカミ, ユタカ
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Kawakami, Yutaka
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慶應義塾大学・医学部・教授
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Research team head
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科研費研究者番号 : 50161287
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塚本, 信夫
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ツカモト, ノブオ
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Tsukamoto, Nobuo
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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 : 20407117
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谷口, 智憲
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ヤグチ, トモノリ
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Yaguchi, Tomonori
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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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2015
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科学研究費補助金研究成果報告書
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2014
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悪性黒色腫では免疫療法が効くが, 効かない症例もあり, 原因として免疫抑制が考えられ, その機序解明は, 治療効果の改善に重要である。本研究では, 低分子化合物・siRNAライブラリーを用いて, ヒト悪性黒色腫細胞に対するT細胞反応の低下や樹状細胞の機能抑制に関与する分子を網羅的にスクリーニングし, 免疫抑制に関与するTGF-βとMAPKシグナルを同定し, その阻害が悪性黒色腫治療に有用であることを示した。
Immunotherapy is now known to be effective on melanoma, but not all the patients. One of the reasons is immunosuppression caused by melanoma cells. Understanding it's mechanism may lead to improvement of melanoma treatment. In this study, by systematic screening of molecules involved in the human melanoma induced immunosuppression using low molecular weight compound libraries and siRNA libraries, we found that TGF-β and MAPK signaling pathways are important for the human melanoma induced immunosuppression in both induction and effector phases of anti-melanoma specific T-cells. We identified cellular and molecular mechanisms in the TGF-β and MAPK induced immunosuppression. These results indicate that blockade of TGF-β or MAPK pathway may be useful for the improvement of current melanoma therapies, particularly for cancer immunotherapy.
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研究種目 : 挑戦的萌芽研究
研究期間 : 2013～2014
課題番号 : 25670506
研究分野 : 腫瘍免疫学
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