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CD115- monocytic myeloid-derived suppressor cells are precursors of OLFM4high polymorphonuclear myeloid-derived

Yunyun Zou1,2, Nobuhiko Kamada3, Seung-Yong Seong4,5

  • 1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

Communications Biology
|March 16, 2023
PubMed

Insights

Researchers discovered a new subtype of monocytic myeloid-derived suppressor cells (M-MDSCs) called CD115- M-MDSCs. These cells are distinct from CD115+ M-MDSCs and show increased plasticity during tumor progression.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Plasticity

Background:

  • Myeloid-derived suppressor cells (MDSCs) are crucial in creating an immunosuppressive tumor microenvironment.
  • MDSCs comprise monocytic (M-MDSCs) and polymorphonuclear (PMN-MDSCs) subtypes.
  • Limited understanding exists regarding MDSC heterogeneity in tumors and across disease stages.

Purpose of the Study:

  • To investigate the phenotypic and functional heterogeneity of M-MDSCs in tumor-bearing hosts.
  • To characterize distinct M-MDSC subsets based on CD115 expression.
  • To explore the role of these subsets in tumor progression and MDSC differentiation.

Main Methods:

  • Subdivision of M-MDSCs based on CD115 expression.
  • Analysis of MDSC populations in bone marrow and blood during tumor progression.
  • Transcriptome analysis to identify gene expression patterns.
  • In vitro differentiation assays.
  • In vivo studies to observe MDSC differentiation in different tissues.

Main Results:

  • CD115- M-MDSCs were identified as functionally distinct from CD115+ M-MDSCs.
  • CD115- M-MDSC populations increased in bone marrow and blood with tumor progression.
  • CD115- M-MDSCs exhibited higher expression of neutrophil-related genes and greater differentiation potential into PMN-MDSCs.
  • CD115- M-MDSCs could differentiate into both OLFM4hi and OLFM4lo PMN-MDSCs, while CD115+ M-MDSCs primarily yielded OLFM4lo PMN-MDSCs.
  • In vivo, M-MDSC to PMN-MDSC differentiation was most common in bone marrow, and M-MDSCs differentiated into tumor-associated macrophages within the tumor.

Conclusions:

  • A previously unrecognized subtype, CD115- M-MDSCs, exists in tumor-bearing hosts.
  • CD115- M-MDSCs display significant cellular plasticity during tumorigenesis.
  • These findings reveal novel insights into MDSC heterogeneity and their dynamic roles in cancer progression.

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