Related Experiment Video

Updated: Jun 6, 2025

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
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Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports

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Targeting CD206+ macrophages disrupts the establishment of a key antitumor immune axis

Arja Ray1,2, Kenneth H Hu1,2, Kelly Kersten1,2

  • 1Department of Pathology, University of California, San Francisco, CA, USA.

The Journal of Experimental Medicine
|November 27, 2024
PubMed

Insights

CD206+ macrophages, often deemed immunosuppressive, actually support anti-tumor immunity by recruiting CD8 T cells and NK cells. Their depletion impairs anti-tumor responses, challenging the M2 macrophage classification.

Area of Science:

  • Immunology
  • Cancer Biology
  • Macrophage Biology

Background:

  • Tumor-associated macrophages (TAMs) expressing CD206 are commonly classified as immunosuppressive M2 macrophages.
  • The precise role of CD206+ TAMs in anti-tumor immunity remains incompletely understood.

Purpose of the Study:

  • To investigate the functional role of CD206+ macrophages and monocytes (Mono/Macs) in the tumor microenvironment.
  • To determine the impact of CD206+ Mono/Mac depletion on immune cell populations and anti-tumor responses.

Main Methods:

  • Development of a novel conditional CD206 (Mrc1) knock-in mouse model for specific visualization and depletion of CD206+ cells.
  • Analysis of immune cell composition, gene expression (CXCL9, Spp1, Cxcr3, Xcl1, Flt3l), and tumor control following CD206+ Mono/Mac depletion.
  • Correlation of CD206 gene signatures with immune cell signatures and patient survival in human cancers.

Main Results:

  • Early depletion of CD206+ Mono/Macs led to indirect loss of cDC1, CD8 T cells, and NK cells in tumors.
  • CD206+ TAMs expressed CXCL9, attracting CD8 T cells, while depleted tumors showed reduced Cxcr3 and Xcl1 expression.
  • A CD206-replete gene signature in human cancers correlated with CD8 T cell, cDC1, and NK cell signatures and better survival.

Conclusions:

  • CD206+ macrophages are not uniformly immunosuppressive and play a crucial role in orchestrating anti-tumor immunity.
  • Disruption of the CD206+ TAM-mediated axis impairs T cell-dependent tumor control.
  • These findings necessitate a re-evaluation of the classification of CD206+ macrophages in cancer immunology.

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