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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Targeting STING to generate therapeutic anti-tumor immunity.
Caroline G Fahey1, Anthony F Cordova2, Patrick C Gedeon3
1Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA; Harvard University, Cambridge, MA, USA.
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is crucial for cancer immunity. Understanding its complex roles in the tumor microenvironment is key to developing effective STING agonist therapies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The cGAS-STING pathway links cytosolic DNA detection to type I interferon production, critical in cancer immunity.
- Clinical translation of STING agonists faces challenges due to model system limitations and the pathway's complexity.
Purpose of the Study:
- To review the multifaceted roles of STING activation within the tumor microenvironment (TME).
- To discuss how current insights can guide the development of novel STING-based cancer immunotherapies.
Main Methods:
- Literature review of STING pathway function in cancer.
- Analysis of STING's context- and cell-type-dependent effects in the TME.
- Evaluation of type I interferon and interferon-independent STING signaling in tumor immunity.
Main Results:
- STING activation yields diverse outcomes in tumor cells, myeloid cells, and T cells within the TME.
- Type I interferon induction by STING can be both pro- and anti-tumorigenic.
- STING signaling possesses emerging interferon-independent functions impacting tumor biology.
Conclusions:
- A comprehensive understanding of STING's complex TME interactions is essential.
- Next-generation STING therapies should leverage these insights to enhance anti-tumor immunity and durability.

