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A spatial map of human macrophage niches reveals context-dependent macrophage functions in colon and breast cancer.
Matusiak, Magdalena; Hickey, John W; Luca, Bogdan; Lu, Guolan; Kidzinski, Lukasz; Zhu, Shirley; Colburg, Deana Rae Crystal; Phillips, Darci J; Brubaker, Sky W; Charville, Gregory W; Shen, Jeanne; Nolan, Garry P; Newman, Aaron M; West, Robert B; van de Rijn, Matt.
Afiliação
  • Matusiak M; Department of Pathology, Stanford University, Stanford, California, USA.
  • Hickey JW; Department of Pathology, Stanford University, Stanford, California, USA.
  • Luca B; Stanford Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, California, USA.
  • Lu G; Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
  • Kidzinski L; Department of Pathology, Stanford University, Stanford, California, USA.
  • Zhu S; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Colburg DRC; Department of Pathology, Stanford University, Stanford, California, USA.
  • Phillips DJ; Department of Pathology, Stanford University, Stanford, California, USA.
  • Brubaker SW; Department of Pathology, Stanford University, Stanford, California, USA.
  • Charville GW; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
  • Shen J; Department of Pathology, Stanford University, Stanford, California, USA.
  • Nolan GP; Department of Pathology, Stanford University, Stanford, California, USA.
  • Newman AM; Department of Pathology, Stanford University, Stanford, California, USA.
  • West RB; Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
  • van de Rijn M; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
Res Sq ; 2023 Jan 10.
Article em En | MEDLINE | ID: mdl-36711732
ABSTRACT
Tumor-associated macrophages (TAMs) display heterogeneous phenotypes. Yet the exact tissue cues that shape macrophage functional diversity are incompletely understood. Here we discriminate, spatially resolve and reveal the function of five distinct macrophage niches within malignant and benign breast and colon tissue. We found that SPP1 TAMs reside in hypoxic and necrotic tumor regions, and a novel subset of FOLR2 tissue resident macrophages (TRMs) supports the plasma cell tissue niche. We discover that IL4I1 macrophages populate niches with high cell turnover where they phagocytose dying cells. Significantly, IL4I1 TAMs abundance correlates with anti-PD1 treatment response in breast cancer. Furthermore, NLRP3 inflammasome activation in NLRP3 TAMs correlates with neutrophil infiltration in the tumors and is associated with poor outcome in breast cancer patients. This suggests the NLRP3 inflammasome as a novel cancer immunetherapy target. Our work uncovers context-dependent roles of macrophage subsets, and suggests novel predictive markers and macrophage subset-specific therapy targets.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article