Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets

Cancer Cell. 2019 Apr 15;35(4):588-602.e10. doi: 10.1016/j.ccell.2019.02.009. Epub 2019 Mar 28.


The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.

Keywords: CCL8; SIGLEC1; breast cancer; endometrial cancer; human circulating monocytes; human macrophages; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cellular Reprogramming*
  • Chemokine CCL8 / genetics
  • Chemokine CCL8 / metabolism
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Molecular Targeted Therapy
  • Monocytes / metabolism*
  • Monocytes / pathology
  • Paracrine Communication*
  • Sialic Acid Binding Ig-like Lectin 1 / genetics
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism
  • Signal Transduction
  • THP-1 Cells
  • Transcription, Genetic*
  • Tumor Microenvironment


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CCL8 protein, human
  • CSF1 protein, human
  • Chemokine CCL8
  • SIGLEC1 protein, human
  • Sialic Acid Binding Ig-like Lectin 1
  • Macrophage Colony-Stimulating Factor