腫瘍関連マクロファージの細胞および分子起源

Ruth A Franklin¹, Will Liao², Abira Sarkar³

¹Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.

Science (New York, N.Y.)

|May 10, 2014

まとめ

マウスの腫瘍関連マクロファージ (TAM) は,他のマクロファージと区別され,乳腺腫瘍の成長を促します. TAMを枯渇させると,抗腫瘍免疫が回復し,腫瘍の進行を阻害し,新しいがん免疫療法標的を提示します.

科学分野:

免疫学免疫学とは
腫瘍学腫瘍学
細胞生物学細胞生物学

背景:

マクロファージは組織ホメオスタシスと免疫に不可欠です.
マクロファージは,がんにおける役割としてますます認識されています.
腫瘍関連マクロファージ (TAMs) は,腫瘍の微小環境内の明確なサブタイプです.

研究の目的:

乳がん腫瘍におけるTAMの起源と機能を調査する.
乳腺組織マクロファージ (MTM) と比較してTAMの特徴を特定する.
ガン免疫療法におけるTAMを標的とした治療の可能性を調査する.

主な方法:

乳がん腫瘍のマウスモデルにおけるTAMとMTMの比較分析.
TAMのフェノタイプ,増殖,および分化経路の評価.
TAMの差異化におけるノッチ信号調節器RBPJの役割に関する調査.
TAM減少が腫瘍の成長とT細胞応答に与える影響の評価.

主要な成果:

乳腺腫瘍の成長は,MTMと異なるTAMの蓄積につながります.
TAMsはVcam1を発現し,炎症性モノサイトから増殖し",代替的に活性化された"フェノタイプを欠いている.
TAMの分化はRBPJに依存する;TAMの枯渇は,細胞毒性T細胞の反応を回復し,腫瘍の成長を抑制する.

結論:

TAMは独特のオントジェニーを持ち,特定の腫瘍誘発の炎症反応によって調節されます.
TAMをターゲットにすることは,がん免疫療法を強化するための有望な戦略です.
TAMの生物学を理解することで,がん治療の新たな道が開けます.

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