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Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy.
Wang, Yu-Chen; Wang, Xi; Yu, Jiaji; Ma, Feiyang; Li, Zhe; Zhou, Yang; Zeng, Samuel; Ma, Xiaoya; Li, Yan-Ruide; Neal, Adam; Huang, Jie; To, Angela; Clarke, Nicole; Memarzadeh, Sanaz; Pellegrini, Matteo; Yang, Lili.
Afiliación
  • Wang YC; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Wang X; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Yu J; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Ma F; Department of Molecular, Cell and Developmental Biology, and Institute for Genomics and Proteomics, University of California, Los Angeles, CA, USA.
  • Li Z; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Zhou Y; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Zeng S; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Ma X; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Li YR; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Neal A; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA.
  • Huang J; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • To A; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Clarke N; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Memarzadeh S; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Pellegrini M; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA.
  • Yang L; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Nat Commun ; 12(1): 3530, 2021 06 10.
Article en En | MEDLINE | ID: mdl-34112755
ABSTRACT
Targeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observe MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibit decreased TAM immunosuppressive functions corresponding with enhanced antitumor immunity. MAOI treatment induces TAM reprogramming and suppresses tumor growth in preclinical mouse syngeneic and human xenograft tumor models. Combining MAOI and anti-PD-1 treatments results in synergistic tumor suppression. Clinical data correlation studies associate high intratumoral MAOA expression with poor patient survival in a broad range of cancers. We further demonstrate that MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Macrófagos Asociados a Tumores / Inmunoterapia / Monoaminooxidasa / Inhibidores de la Monoaminooxidasa / Neoplasias Tipo de estudio: Risk_factors_studies Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Macrófagos Asociados a Tumores / Inmunoterapia / Monoaminooxidasa / Inhibidores de la Monoaminooxidasa / Neoplasias Tipo de estudio: Risk_factors_studies Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos