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低糖質高脂肪食ががん性腹膜炎の進行に及ぼす影響

ワトキンス, 彩子 東京大学 DOI:10.15083/0002007108

2023.03.24

概要

[課程-2]
審査の結果の要旨
氏名ワトキンス 彩子
本研究は、進行がん患者の体重維持や高血糖予防に有効とされる低糖質高脂肪食が、宿
主の免疫反応およびがんの進行に及ぼす影響を明らかにするため、マウス Panc02 がん性
腹膜炎モデルを用いて検討を行ったものであり、下記の結果を得ている。
1. 飽和脂肪酸と一価不飽和脂肪酸を含むラード強化の低糖質高脂肪食を与えたマウスで
は、通常食と比較して播種腫瘤の増悪、生存が低下した。腹膜播種が形成された時点
の腹腔洗浄液中と腫瘤中では、制御性 T 細胞および M2 型マクロファージが高値を示
した。この結果よりラード強化の低糖質高脂肪食は、マウスの抗腫瘍性の免疫を強く
抑制し、がん促進性に働く可能性が示された。
2. n-6 系多価不飽和脂肪酸(n-6 系 PUFA)を主に含む大豆油強化の低糖質高脂肪食を与
えたマウスでは、通常食と比較して生存が低下した。腹膜播種が形成された時点の腹
腔洗浄液中または腫瘤中で、マクロファージの M1/M2 比の低下と CD8 陽性 T 細胞上
の PD-1受容体の発現が高値を示した。さらに抗腫瘍性に働くインターロイキン 12、
インターフェロンγ、CD8 陽性 T 細胞数、ナチュラルキラー細胞数が低値を示した。
これらの機序の一因に、n-6 系 PUFA 摂取量増加に伴う腫瘤中のシクロオキシゲナー
ゼ 2 の発現上昇が考えられた。上記の結果より大豆油強化の低糖質高脂肪食は、特に
抗腫瘍性免疫を減弱し、がん促進性に働く可能性が示された。
3. 大豆油と魚油を n-6 系 PUFA:n-3 系 PUFA=2:1 になるように調整した低糖質高脂肪食
を与えたマウスでは、播種腫瘤の総重量は他の低糖質高脂肪食群および通常食群と比
較して低値を示し、生存にも悪影響を及ぼさなかった。腫瘤中の細胞外シグナル調節
キナーゼ、核内因子κB、低酸素誘導因子の発現が低下し、抗腫瘍性のサイトカインレ
ベルおよび免疫細胞数が維持された。その機序の一つに血漿アディポネクチンレベル
の上昇が考えられた。この結果より、魚油を強化した低糖質高脂肪食では炎症や免疫
抑制などのがん細胞の増殖に有利な環境が、他の低糖質高脂肪食を摂食したマウスの
ように形成されず、抗腫瘍免疫を維持できる可能性が示された。
以上、本論文は低糖質高脂肪食でも脂肪の種類によってはがんの進行を促進する一方で、
n-6 系 PUFA:n-3 系 PUFA=2:1 に調整した低糖質高脂肪食は、代謝の点のみならず

抗炎症・がん免疫維持の点からがん患者の栄養療法として有効である可能性を示した。
進行がん患者の栄養療法について研究が少ないなかで、低糖質高脂肪食ががん病態の生体
反応と予後に及ぼす意義について重要な知見を得られたと考えている。
よって本論文は博士( 医学 )の学位請求論文として合格と認められる。

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