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研究分野生物医学と臨床科学腫瘍学とがん発生血液学的腫瘍
組織に定着するマクロファージは,初期のNSCLC細胞にプロトーマージンニッチを提供する.

組織に定着するマクロファージは,初期のNSCLC細胞にプロトーマージンニッチを提供する.

María Casanova-Acebes ^1,2,3,4, Erica Dalla ^5,6,7,8, Andrew M Leader ^9,10,11, Jessica LeBerichel ^9,10,11, Jovan Nikolic ¹², Blanca M Morales ¹³, Markus Brown ¹³, Christie Chang ^9,10,11, Leanna Troncoso ^9,10,11, Steven T Chen ^9,10,11, Ana Sastre-Perona ^14,15, Matthew D Park ^9,10,11, Alexandra Tabachnikova ^9,10,11, Maxime Dhainaut ^10,11,16, Pauline Hamon ^9,10,11, Barbara Maier ^9,10,11,17, Catherine M Sawai ¹⁸, Esperanza Agulló-Pascual ¹⁹, Markus Schober ¹⁴, Brian D Brown ^10,11,16,20, Boris Reizis ²¹, Thomas Marron ^9,10,11,5,22, Ephraim Kenigsberg ^10,20, Christine Moussion ¹³, Philippe Benaroch ¹², Julio A Aguirre-Ghiso ^{9,10,11,5,6,7,8}, Miriam Merad ^23,24,25,26

María Casanova-Acebes ^1,2,3,4, Erica Dalla ^5,6,7,8, Andrew M Leader ^9,10,11

¹Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. mcasanova@cnio.es.
²Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. mcasanova@cnio.es.
³Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. mcasanova@cnio.es.
⁴Cancer Immunity Laboratory, Molecular Oncology Program, Spanish National Cancer Centre, Madrid, Spain. mcasanova@cnio.es.
⁵Division of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁹Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁰Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹²Institut Curie, PSL Research University, INSERM U932, Paris, France.
¹³Department of Cancer Immunology, Genentech, South San Francisco, CA, USA.
¹⁴The Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, NY, USA.
¹⁵Experimental Therapies and Novel Biomarkers in Cancer, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.
¹⁶Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁷CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
¹⁸INSERM U1218 ACTION, University of Bordeaux, Bordeaux, France.
¹⁹Microscopy CoRE, Dean's CoREs, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁰Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²¹Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA.
²²Institute of Thoracic Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²³Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. miriam.merad@mssm.edu.
²⁴Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. miriam.merad@mssm.edu.
²⁵Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. miriam.merad@mssm.edu.
²⁶Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. miriam.merad@mssm.edu.

⁰Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. mcasanova@cnio.es.

Nature +

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2021年6月17日

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PubMedで要約を見る

まとめ

この要約は機械生成です。

組織に宿るマクロファージは,腫瘍の侵入性と免疫回避を助長することで,早期の肺がんを促進します. これらのマクロファージをターゲットにすることで早期の肺がんを予防し治療する新しい戦略が生まれます

科学分野

免疫学
腫瘍学
細胞生物学

背景

マクロファージは腫瘍の微小環境 (TME) で重要な役割を果たし,腫瘍の免疫性と免疫療法への反応に影響を与えます.
腫瘍内のマクロファージの多様性を理解することは効果的ながん治療の開発に不可欠です
マクロファージは異なる系統から生じる:自己再生する組織居住マクロファージと短命の単細胞由来マクロファージ.

研究の目的

人間の非小細胞肺がん (NSCLC) の腫瘍におけるマクロファージ集団の多様性と起源を調査する.
肺がんの早期進行における組織在住マクロファージと単細胞由来のマクロファージの異なる役割を解明する.
マクロファージ区間の早期肺がんの潜在的治療標的を特定する.

主な方法

人間のNSCLCの病変からの腫瘍関連白血球の単細胞RNAシーケンシング.
マクロファージの起源と分布を決定するためにマウスモデルでの系統追跡.
組織に居住するマクロファージの枯渇を含む機能的研究.

主要な成果

人間の肺腫瘍とマウスの肺腫瘍では,異なるマクロファージ集団が特定され,TME内で起源と分布が異なっていた.
組織内マクロファージは腫瘍発達の初期に蓄積し,腫瘍細胞の侵入性を促進し,調節性T細胞を通じて適応免疫を抑制する.
組織内マクロファージの枯渇により,調節性T細胞が減少し,CD8+T細胞の蓄積が増加し,腫瘍の成長と侵入性が低下した.
単細胞由来マクロファージはNSCLCの後期段階で支配的になり,組織内マクロファージは腫瘍周辺に再分布する.

結論

組織に宿るマクロファージは肺がんの早期発症と進行を促す主要な要因です
これらのマクロファージは腫瘍の侵入性や免疫回避性を促進し,早期NSCLCの有望な治療標的となっています.
組織に宿るマクロファージをターゲットにすることで肺がんの早期病変の予防と治療に新しい戦略が生まれます

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