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「第1相試験:セリンおよびグリシン不使用の食事が大腸癌における免疫応答を向上させる」

iLIFE by iLIFE
2024年11月30日
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「第1相試験:セリンおよびグリシン不使用の食事が大腸癌における免疫応答を向上させる」
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**専門的な食事が大腸癌患者の免疫細胞活性を高め、免疫療法の効果を改善することを示す初期試験**

2024年11月29日、医学博士リジ・トーマスによる研究がダニエル・エリス(B.Sc.)によってレビューされました。

大腸癌(CRC)は、世界の癌による死亡原因の中で3位にランクされており、死亡者数は増加しています。免疫チェックポイント阻害剤(ICIs)は、これらの腫瘍に対して効果が薄いことが示されています。最近の『Cell Metabolism』に掲載された研究では、セリン/グリシンフリーの食事が腫瘍の成長に与える影響、特にICIs療法に関して調査されています。

背景として、ICIsは大腸癌の治療に承認されていますが、プログラム死-1(PD-1)阻害剤と呼ばれる一群の免疫療法薬は、CRC患者において効果が低いことが示されています。ミスマッチ修復が正常でマイクロサテライト安定(pMMR/MSS)特性を持つ患者のうち、わずか15%がこの治療の恩恵を受けています。一方、ミスマッチ修復欠損およびマイクロサテライト不安定(d-MMR/MSI-H)CRC患者は、PD-1阻害剤に完全に反応します。これには、腫瘍の新抗原発現の増加と腫瘍への免疫細胞の浸潤が含まれます。免疫状態や腫瘍微小環境を変えることで、免疫療法の効果を高めることができる可能性があります。その一つの方法は、腫瘍から栄養素を奪うことです。

癌細胞は高い代謝率を持ち、癌のライフサイクル全体を通じてセリン、グリシン、その他のアミノ酸を消費します。この供給は腫瘍の免疫逃避にも重要です。癌細胞はエネルギーのためにグルコースの嫌気的分解に依存し、大量の乳酸を生成します。高濃度の乳酸は免疫抑制的な腫瘍微小環境(TME)を誘発します。腫瘍関連マクロファージはM2表現型にシフトし、CD8+ Tリンパ球やナチュラルキラー(NK)細胞は細胞傷害性から離れ、細胞媒介の抗腫瘍免疫が損なわれます。乳酸はまた、腫瘍内の制御性T細胞(Treg)の活性を高め、抗腫瘍免疫応答を調整します。

これまでの研究では、セリン/グリシンフリーの食事(-SG食)の影響が探求されてきましたが、これが大腸癌(CRC)の発生率や死亡率にどのように影響するかはあまり知られていませんでした。このことが、-SG食がCRCの成長と細胞媒介の抗腫瘍免疫に与える影響を調査する現在の研究を促しました。

– SG食は腫瘍の成長を抑制する

この研究では、-SG食が培養中のCRC細胞の成長を抑制することが示されました。抗増殖効果は、細胞の合成期への移行の遅延と結びついていました。

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