# Immune Regulation of Gastric Cancer

> **NIH NIH P20** · WEST VIRGINIA UNIVERSITY · 2024 · $259,173

## Abstract

ABSTRACT - Immune Regulation of Gastric Cancer
Gastric cancer is the 4th leading cause of cancer deaths worldwide. Over 90% of gastric cancers are associated
with long-term Helicobacter pylori infection. However, the infection alone has limited pathogenic effects on the
gastric mucosa. Rather, the infection triggers massive gastric inflammation, which becomes increasingly hyper-
active, damaging the stomach and creating the requisite environment for carcinogenesis. However, the mecha-
nisms and pathways that regulate the onset of hyperactive inflammation are unknown. Glucocorticoids are potent
anti-inflammatory steroid hormones produced by the adrenal glands. We have shown that glucocorticoids are
critical for suppressing pathogenic gastric inflammation. Adrenalectomized mice spontaneously develop massive
gastric inflammation driving a potentially pre-neoplastic condition called Spasmolytic polypeptide-expressing
metaplasia (SPEM). Glucocorticoid signaling is also disrupted in gastric cancers, but the role of these hormones
in gastric cancer development and progression has not been studied. The overall goal of this proposal is to
establish the role of glucocorticoids in preventing Helicobacter-induced gastric cancer development. Our prelim-
inary data suggest that endogenous glucocorticoids are critical regulators of the gastric inflammatory response
to Helicobacter infection. Loss of glucocorticoid signaling accelerates gastric epithelial damage, metaplasia, and
dysplasia. Thus, the loss of glucocorticoid signaling likely accelerates Helicobacter-induced gastric cancer de-
velopment. However, glucocorticoid protection from gastric cancer development has never been studied. Spe-
cific Aim 1 will examine how glucocorticoid signaling regulates gastric T cell activation and polarization. Specific
Aim 2 will examine how long-term Helicobacter infection disrupts endogenous glucocorticoid signaling within the
stomach, promoting hyperactive inflammation even upon Helicobacter eradication. Specific Aim 3 will utilize the
INS-GAS mouse model of gastric carcinogenesis to study whether glucocorticoid signaling protects from gastric
cancer development. Moreover, we will use fresh tumor samples to examine how glucocorticoid signaling mod-
ulates the tumor microenvironment in humans. These studies will be the first to investigate how glucocorticoid
signaling regulates gastric cancer development. Ultimately, the knowledge generated here will facilitate the
launch of human studies and the development of novel diagnostic and therapeutic strategies to prevent gastric
cancer.

## Key facts

- **NIH application ID:** 10916369
- **Project number:** 5P20GM121322-07
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Jonathan Busada
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $259,173
- **Award type:** 5
- **Project period:** 2018-08-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916369

## Citation

> US National Institutes of Health, RePORTER application 10916369, Immune Regulation of Gastric Cancer (5P20GM121322-07). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10916369. Licensed CC0.

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