# Enhancing the antitumor effect of radiation therapy by targeting the cGAS-STING pathway

> **NIH NIH F99** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $37,263

## Abstract

Project Summary and Abstract
Immunotherapy has achieved promising outcomes in cancer treatments; however, most patients still do not
respond to the current therapies. There are several critical gaps in our current knowledge of what types of
immune cells exist in the tumor microenvironment and how their presence (or absence) impacts the tumor
immune surveillance. My long-term goal is to develop new cancer prevention and treatment approaches through
dissecting the diverse immune cells and their roles in the tumor microenvironment. My preliminary studies have
identified an enhanced antitumor effect for metastatic cancers by combining radiotherapy with the innate immune
sensing pathway activation (the cGAS-cGAMP-STING pathway). This proposal aims to identify novel immune
cell populations that contribute to the effective antitumor treatment strategy. The central hypothesis is that
specific subsets of immune cells induced by this treatment strategy are the major factors controlling tumor
treatment effects. Successful identification of these immune cell populations will improve our understanding of
antitumor immunity and cancer immunotherapies.
I will test the central hypothesis by pursuing two specific aims: 1) Characterize the immune cell heterogeneity in
tumors in response to STING activation (F99 phase); 2) Elucidate the mechanism of abscopal antitumor effects
achieved through the combination of cGAMP and radiotherapy (K00 phase). I will pursue these aims using an
innovative combination of experimental and computational techniques. I will use unbiased single-cell
transcriptome data analysis to identify novel cell populations critical for the tumor treatments and investigate their
functions in mouse models. The proposed research is significant because the unbiased genomics data allows
me to identify new mechanisms that may have a broad implication in other tumor types and aid in developing
new therapeutic strategies. This work will also develop resources that can be used by other researchers in the
cancer immunology field. The expected outcome of this work is: 1) identifying novel immune cell populations with
antitumor function, 2) offering rational combination strategies to improve antitumor effects, 3) informing the
design of cancer vaccines. This project will advance cancer immunology fields by providing new therapeutic
strategies for metastatic cancers. In addition, the skills and expertise obtained from both phases will prepare me
to become an independent researcher in cancer immunology.

## Key facts

- **NIH application ID:** 10529042
- **Project number:** 1F99CA274647-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Yan Fang
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,263
- **Award type:** 1
- **Project period:** 2022-07-11 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10529042

## Citation

> US National Institutes of Health, RePORTER application 10529042, Enhancing the antitumor effect of radiation therapy by targeting the cGAS-STING pathway (1F99CA274647-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10529042. Licensed CC0.

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