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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cassetta, L; Fragkogianni, S; Sims, AH; Swierczak, A; Forrester, LM; Zhang, H; Soong, DYH; Cotechini, T; Anur, P; Lin, EY; Fidanza, A; Lopez-Yrigoyen, M; Millar, MR; Urman, A; Ai, Z; Spellman, PT; Hwang, ES; Dixon, JM; Wiechmann, L; Coussens, LM; Smith, HO; Pollard, JW

Published Date

  • April 15, 2019

Published In

Volume / Issue

  • 35 / 4

Start / End Page

  • 588 - 602.e10

PubMed ID

  • 30930117

Pubmed Central ID

  • 30930117

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2019.02.009

Language

  • eng

Conference Location

  • United States