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Updated: Jun 16, 2025
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Immunometabolic Circuits in Infection for Advancing Host Directed Therapies
Published on: September 13, 2024
379
An Immunometabolic Route for Activating cGAS/STING to Drive Anticancer Immunity
Francisca Borges1, Abhishek D Garg1
1Cell Stress and Immunity (CSI) Laboratory, Department for Cellular and Molecular Medicine (CMM), KU Leuven, Leuven, Belgium.
Cancer Research
|August 15, 2024
Summary
Serine deprivation triggers the cGAS/STING pathway, enhancing antitumor immunity. This metabolic strategy shows promise for cancer therapy, boosting immune responses and improving patient survival when combined with PD1 blockade.
Area of Science:
- Immunology
- Metabolic pathways
- Cancer biology
Background:
- The cGAS/STING pathway is vital for innate immune responses against cancer.
- Serine, an essential amino acid, impacts tumor growth and immune surveillance.
- Mitochondrial DNA (mtDNA) release can activate immune signaling pathways.
Purpose of the Study:
- To investigate the effect of serine deprivation on the cGAS/STING pathway.
- To explore the potential of serine deprivation as an anticancer therapy.
- To evaluate the combination of serine deprivation with immune checkpoint inhibitors.
Main Methods:
- Inducing serine deprivation in cellular and mouse models.
- Measuring mitochondrial dysfunction and mtDNA release.
- Assessing immune cell infiltration and type I Interferon (IFN) responses.
- Analyzing clinical data for serine enrichment signatures in colorectal cancer.
Main Results:
- Serine deprivation leads to mitochondrial dysfunction and mtDNA release, activating the cGAS/STING pathway.
- This activation induces type I IFN responses and enhances antitumor immunity, including CD4+/CD8+ T cell infiltration.
- Lower serine enrichment in colorectal cancer patients correlates with immune activation and better survival.
- Combining serine deprivation with PD1 blockade significantly reduces tumor volume and establishes long-term immunity in mice.
Conclusions:
- Serine deprivation is a viable strategy to activate the cGAS/STING pathway and bolster antitumor immunity.
- This approach enhances the efficacy of immune checkpoint blockade therapies.
- Serine metabolism modulation offers a promising avenue for improving cancer treatment outcomes.
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