IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function
Moshe Elkabets1, Vera S G Ribeiro, Charles A Dinarello
1Innate Immunity Unit, Institut Pasteur, Paris, France.
European Journal of Immunology
|November 27, 2010
Summary
Chronic inflammation drives cancer progression by promoting myeloid-derived suppressor cells (MDSC). A novel subset of IL-1β-induced MDSC, lacking Ly6C expression, impairs anti-tumor immunity, suggesting new therapeutic targets.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Chronic inflammation promotes cancer development and progression.
- Myeloid-derived suppressor cells (MDSC) accumulate in tumors, suppressing anti-tumor immune responses.
- Tumor-derived Interleukin-1 beta (IL-1β) induces MDSC accumulation and enhances their T cell-suppressive function.
Purpose of the Study:
- To identify the specific mechanisms by which IL-1β-induced MDSC enhance tumor progression.
- To characterize a novel subset of MDSC responsible for increased immune suppression.
- To investigate the functional impact of this novel MDSC subset on anti-tumor immunity.
Main Methods:
- Analysis of MDSC populations in tumor-bearing mice under varying inflammatory conditions.
- Characterization of MDSC subsets based on Ly6C expression.
- In vitro and in vivo assessment of Ly6C(neg) MDSC effects on Natural Killer (NK) cell development and function.
Main Results:
- A novel subset of MDSC, defined by the absence of Ly6C expression (Ly6C(neg) MDSC), was identified.
- Ly6C(neg) MDSC were predominant under IL-1β-induced inflammatory conditions.
- Ly6C(neg) MDSC were found to impair both the development and function of NK cells in vitro and in vivo.
Conclusions:
- IL-1β induces a distinct subset of MDSC (Ly6C(neg)) with potent immune-suppressive properties.
- Ly6C(neg) MDSC contribute to tumor progression by inhibiting NK cell-mediated anti-tumor immunity.
- Targeting Ly6C(neg) MDSC represents a potential therapeutic strategy for cancer treatment.
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