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A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
Published on: January 9, 2018
Peripheral 4-1BB signaling negatively regulates NK cell development through IFN-gamma
Beom K Choi1, Young H Kim, Chang H Kim
1Division of Cell and Immunobiology, National Cancer Center, 809 Madu, Ilsan, Goyang, Kyounggi-do 411-769, Korea.
Journal of Immunology (Baltimore, Md. : 1950)
|July 9, 2010
Summary
Stimulating 4-1BB (CD137) enhances anticancer immunity primarily through CD8(+) T cells, while its absence boosts natural killer (NK) cell activity. This indicates 4-1BB signaling shifts immune response from NK cells to CD8(+) T cells.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Immunology
Background:
- 4-1BB (CD137) stimulation demonstrates potent anticancer effects in vivo.
- Conversely, 4-1BB-deficient mice exhibit resistance to tumor growth, suggesting complex regulatory mechanisms.
Purpose of the Study:
- To elucidate the mechanisms behind the contrasting roles of 4-1BB signaling in tumor immunity.
- To investigate the interplay between CD8(+) T cells, NK cells, and 4-1BB in antitumor responses.
Main Methods:
- Comparative analysis of tumor growth and immune cell populations in wild-type and 4-1BB-deficient mice.
- Flow cytometry to assess frequencies and numbers of splenic and bone marrow immune cells.
- Evaluation of the role of interferon-gamma (IFN-γ) in 4-1BB-mediated immune modulation.
Main Results:
- Therapeutic 4-1BB triggering relied on CD8(+) T cells and NK cells for anticancer effects.
- Absence of 4-1BB signaling required both CD8(+) T and NK cells for tumor suppression.
- 4-1BB signaling decreased NK cell numbers in spleen and bone marrow, a process dependent on IFN-γ.
- IFN-γ, produced by CD8(+) T and NK cells, mediated NK cell development suppression in the bone marrow.
Conclusions:
- 4-1BB signaling orchestrates a shift in antitumor immunity, favoring adaptive CD8(+) T cells over innate NK cells.
- Interferon-gamma (IFN-γ) levels are critical regulators of this 4-1BB-mediated immune cell balance.
- Understanding this balance is key for optimizing cancer immunotherapy strategies.
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