Macrophages of distinct origins contribute to tumor development in the lung

J Exp Med. 2018 Oct 1;215(10):2536-2553. doi: 10.1084/jem.20180534. Epub 2018 Sep 10.


Tissue-resident macrophages can self-maintain without contribution of adult hematopoiesis. Herein we show that tissue-resident interstitial macrophages (Res-TAMs) in mouse lungs contribute to the pool of tumor-associated macrophages (TAMs) together with CCR2-dependent recruited macrophages (MoD-TAMs). Res-TAMs largely correlated with tumor cell growth in vivo, while MoD-TAMs accumulation was associated with enhanced tumor spreading. Both cell subsets were depleted after chemotherapy, but MoD-TAMs rapidly recovered and performed phagocytosis-mediated tumor clearance. Interestingly, anti-VEGF treatment combined with chemotherapy inhibited both Res and Mod-TAM reconstitution without affecting monocyte infiltration and improved its efficacy. Our results reveal that the developmental origin of TAMs dictates their relative distribution, function, and response to cancer therapies in lung tumors.

Publication types

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

MeSH terms

  • Animals
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Macrophages / immunology*
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Monocytes / immunology*
  • Monocytes / pathology
  • Phagocytosis*
  • Receptors, CCR2 / immunology


  • Ccr2 protein, mouse
  • Receptors, CCR2