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A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
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Tumor cGAMP Awakens the Natural Killers
Shriram K Sundararaman1, David A Barbie1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Immunity
|October 18, 2018
Summary
Tumor cells release 2'3'-cGAMP, activating the STING pathway in surrounding cells. This triggers type I interferon production, enhancing natural killer cell activity against tumors.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Type I interferons (IFN) are crucial for anti-tumor immunity.
- The tumor microenvironment (TME) significantly influences immune responses to cancer.
Purpose of the Study:
- To investigate the source and mechanism of type I IFN production in the TME.
- To elucidate how tumor cells communicate with immune cells to initiate anti-tumor responses.
Main Methods:
- Analysis of tumor cell-derived molecules.
- Investigating the STING signaling pathway activation in non-tumor cells.
- Assessing natural killer (NK) cell function and tumor rejection.
Main Results:
- Tumor cells were found to produce 2',3'-cGAMP.
- 2',3'-cGAMP activates the STING pathway in adjacent non-tumor cells.
- STING activation leads to type I IFN production and primes NK cells for tumor rejection.
Conclusions:
- Tumor-derived 2',3"-cGAMP is a key mediator of anti-tumor immunity.
- The STING pathway in non-tumor cells is essential for initiating type I IFN-driven anti-tumor responses.
- Targeting this pathway could enhance cancer immunotherapy.
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