# The impact of exposure to allergic inflammation on esophageal carcinogenesis

> **NIH NIH R21** · TEMPLE UNIV OF THE COMMONWEALTH · 2022 · $181,543

## Abstract

Project Summary
Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer mortality worldwide.
Chronic reflux-associated esophagitis, termed gastroesophageal reflux disease (GERD), is a primary risk
factor for development of esophageal adenocarcinoma. Eosinophilic esophagitis (EoE) represents food
allergen-mediated esophagitis characterized by esophageal eosinophilia. In contrast to patients with reflux
esophagitis, epidemiological data indicates that EoE patients fail to develop esophageal cancer despite the
presence of chronic esophageal inflammation. A negative correlation between allergic inflammation and cancer
risk has been identified in a variety of organs via population-based studies; however, functional investigations
are necessary to define the relationship between allergy and cancer as well as to determine the feasibility of
approaches for leveraging allergic inflammation to improve clinical outcomes in cancer patients. To examine
the relationship between EoE and cancer, we paired murine models of the two conditions. Our robust
preliminary data indicate that exposure to EoE inflammation limits esophageal carcinogenesis in vivo. We
hypothesize that EoE inflammation limits esophageal carcinogenesis by activating anti-tumor responses in the
immune and epithelial cell compartments. We will test this hypothesis by pursuing the following Specific Aims:
Aim 1: Identify the immune-mediated mechanisms responsible for tumor cell apoptosis induced by EoE
inflammation. Aim 2: Delineate the impact of EoE inflammation upon esophageal epithelial cells in the context
of carcinogenesis. These studies provide the first functional investigation of the relationship between EoE and
esophageal cancer with the potential to unveil novel mechanisms for targeting the allergic immune response
and/or allergy-mediated esophageal epithelial fate decisions to improve clinical care for cancer patients. These
developmental R21 studies will identify the direct cellular/molecular mechanisms through which the EoE
influences the epithelial and immune cell compartments to limit esophageal carcinogenesis. A future R01
proposal will aggressively pursue identified mechanisms in preclinical and clinical models to meet our long-
term goal of defining novel strategies for improving esophageal cancer prevention, diagnosis, monitoring, and
therapy. As a negative association between allergic inflammation and cancer has been identified in various
organs, findings from this study may have broad implications for cancer prevention and therapy.

## Key facts

- **NIH application ID:** 10308094
- **Project number:** 5R21CA256465-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Kelly A Whelan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $181,543
- **Award type:** 5
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308094

## Citation

> US National Institutes of Health, RePORTER application 10308094, The impact of exposure to allergic inflammation on esophageal carcinogenesis (5R21CA256465-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10308094. Licensed CC0.

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