Cell Reports
Volume 33, Issue 13, 29 December 2020, 108571
Journal home page for Cell Reports

Article
Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer

https://doi.org/10.1016/j.celrep.2020.108571Get rights and content
Under a Creative Commons license
open access

Highlights

  • M-MDSCs, in contrast to monocytes, differentiate into immune-suppressive macrophages

  • M-MDSC-derived macrophages fail to downregulate expression of S100A8/A9 proteins

  • High expression of S100A9 regulates suppressive activity of macrophages via C/EBPβ

  • S100A9+ macrophages are associated with negative clinical outcome in cancer patients

Summary

Here, we report that functional heterogeneity of macrophages in cancer could be determined by the nature of their precursors: monocytes (Mons) and monocytic myeloid-derived suppressor cells (M-MDSCs). Macrophages that are differentiated from M-MDSCs, but not from Mons, are immune suppressive, with a genomic profile matching that of M-MDSCs. Immune-suppressive activity of M-MDSC-derived macrophages is dependent on the persistent expression of S100A9 protein in these cells. S100A9 also promotes M2 polarization of macrophages. Tissue-resident- and Mon-derived macrophages lack expression of this protein. S100A9-dependent immune-suppressive activity of macrophages involves transcription factor C/EBPβ. The presence of S100A9-positive macrophages in tumor tissues is associated with shorter survival in patients with head and neck cancer and poor response to PD-1 antibody treatment in patients with metastatic melanoma. Thus, this study reveals the pathway of the development of immune-suppressive macrophages and suggests an approach to their selective targeting.

Keywords

tumor immunology
myeloid-derived suppressor cells
tumor associated macrophages
S100A9
immune suppression

Cited by (0)

7

Current address: Charisma Therapeutics, Philadelphia, PA 19104, USA

8

Current address: Syndax Pharmaceuticals, Waltham, MA 02451, USA

9

These authors contributed equally

10

Lead Contact