# Identifying Mechanisms of Paracrine cGAMP Signaling in the Tumor Microenvironment

> **NIH NIH F30** · STANFORD UNIVERSITY · 2021 · $38,222

## Abstract

Abstract
While cancer immunotherapy targeting the adaptive immune system has led to prolonged disease-free survival
in otherwise terminal patients, there are few effective cancer therapies that target the innate immune system.
However, there is mounting evidence that the cGAMP-STING innate immunity pathway is a promising anti-
cancer target. While cGAMP is synthesized and functions inside the cytoplasm, recent evidence has shown that
cGAMP is exported by cancer cells and imported by cGAMP-sensing responder cells in the host, thereby acting
as a paracrine immunotransmitter. However, the mechanisms by which cancer cells export cGAMP into the
extracellular space and responder cells import cGAMP to activate intracellular STING are unclear. We previously
described the reduced folate carrier SLC19A1 as the first known importer of cGAMP and other cyclic
dinucleotides; however, it has not yet been demonstrated to play a physiological role within the tumor
microenvironment. Likewise, the identities of the cGAMP exporter and the cGAMP-sensing responder cell
populations remain unknown.
The goal of this proposal is to further our understanding of cGAMP import and export in cancer. First, I will
determine the role of SLC19A1 as a cGAMP importer in vivo using murine models of breast cancer. Then, I will
confirm that our candidate cGAMP exporter, the xenobiotic exporter ABCG2, exports cGAMP in vitro in cell
culture and in vivo in tumor models. Finally, I will demonstrate that intratumoral extracellular cGAMP induces
host immune activation, and I will identify the initial cGAMP-sensing responder cells within the tumor
microenvironment. This research will provide insight into cGAMP's role as an immunotransmitter and will
advance the current model of how cGAMP activates the immune system in response to cancer, leading to
novel targets for therapeutic intervention.

## Key facts

- **NIH application ID:** 10145485
- **Project number:** 5F30CA250145-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Anthony Frank Cordova
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,222
- **Award type:** 5
- **Project period:** 2020-07-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145485

## Citation

> US National Institutes of Health, RePORTER application 10145485, Identifying Mechanisms of Paracrine cGAMP Signaling in the Tumor Microenvironment (5F30CA250145-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145485. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*