AI Article Synopsis

  • A new subset of macrophages called iron-rich tumor-associated macrophages (iTAMs) was identified, marked by high levels of intracellular iron and involvement in angiogenesis and immunosuppression in tumors.
  • Two types of iTAMs were characterized based on their location and gene expression: perivascular (pviTAM) and stromal (stiTAM).
  • The endothelin receptor type B (Ednrb) was identified as a specific marker for iTAMs, and its deletion reduced tumor growth, while the transcription factor Bach1 was found to regulate iTAM functions by inhibiting Ednrb expression.

Article Abstract

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional program, including Ednrb expression. Heme is a known inhibitor of Bach1, and, correspondingly, heme exposure induced Ednrb and iTAM signature genes in macrophages. Thus, iTAMs are a distinct macrophage subset regulated by the transcription factor Bach1 and characterized by Ednrb-mediated immunosuppressive and angiogenic functions.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457473PMC
http://dx.doi.org/10.1084/jem.20230420DOI Listing

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