Related Experiment Video
Updated: May 9, 2026

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
Tumor microenvironmental conversion of natural killer cells into myeloid-derived suppressor cells
Young-Jun Park1, Boyeong Song, Yun-Sun Kim
1Authors' Affiliations: Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy; WCU, Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University; Neonatal Vaccinology Section, International Vaccine Institute, SNU Research Park; and Laboratory of Microbiology and Immunology, College of Pharmacy, Inje University, Gimhae, Gyungnam, Korea.
Abstract:
How myeloid-derived suppressor cells (MDSC) emerge in the tumor environment remains unclear. Here, we report that GM-CSF can convert natural killer (NK) cells into MDSCs. When transferred into tumor-bearing mice, adoptively transferred NK cells lost their NK phenotype and were converted into Ly6C(high)Ly6G(high) MDSC. This conversion was abolished by exposure to IL-2 either in vitro or in vivo. Notably, we found that of the 4 maturation stages based on CD11b/CD27 expression levels, only the CD11b(high)CD27(high) NK cells could be converted into CD11b(+)Gr1(+) MDSC ex vivo. Transfer of CD27(high) NK cells from tumor-bearing mice into tumor-bearing recipients was associated with conversion to MDSC in a manner associated with reduced numbers of CD11b(high)CD27(high) and CD11b(high)CD27(low) NK cell populations in the recipients. Our results identify a pathway of MDSC development from immature NK cells in tumor-bearing hosts, providing new insights into how tumor cells modulate their host immune microenvironment to escape immune surveillance.
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) converts natural killer (NK) cells into myeloid-derived suppressor cells (MDSC). Interleukin-2 (IL-2) prevents this conversion, offering new insights into tumor immune evasion.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Biology
Background:
- The mechanisms by which myeloid-derived suppressor cells (MDSC) develop within the tumor microenvironment are not fully understood.
- MDSCs play a critical role in suppressing anti-tumor immunity and promoting tumor progression.
Purpose of the Study:
- To investigate the potential of natural killer (NK) cells to differentiate into MDSCs.
- To identify the specific NK cell populations and factors involved in this conversion process.
Main Methods:
- Adoptive transfer of NK cells into tumor-bearing mice.
- In vitro and in vivo treatment with cytokines (GM-CSF and IL-2).
- Flow cytometry analysis of NK cell phenotype and maturation markers (CD11b, CD27, Ly6C, Ly6G).
Main Results:
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) induced the conversion of NK cells into MDSCs (Ly6C(high)Ly6G(high)).
- Interleukin-2 (IL-2) inhibited this NK cell to MDSC conversion.
- Immature NK cells (CD11b(high)CD27(high)) were identified as the specific subset capable of differentiating into MDSCs (CD11b(+)Gr1(+)) ex vivo.
Conclusions:
- Immature NK cells represent a novel source of MDSCs in tumor-bearing hosts.
- This pathway highlights a mechanism by which tumors may manipulate the immune microenvironment to evade immune surveillance.
- Targeting NK cell differentiation could offer new therapeutic strategies against cancer.
Related Concept Videos
The Tumor Microenvironment
The Tumor Microenvironment
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
