Abstract 1752: Exploring the relation of eosinophilic esophagitis (EoE) with esophageal cancer

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 and determine the feasibility of therapeutic approaches leveraging allergic inflammation for cancer prevention and therapy. Esophageal cancer is amongst the most aggressive forms of human cancer. Reflux esophagitis is a primary risk factor for esophageal adenocarcinoma. Eosinophilic esophagitis (EoE) represents a distinct, food allergen-mediated type of 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. To investigate the functional relationship between EoE and esophageal cancer, we have paired the food allergen-driven MC903/Ovalbumin (OVA) model of EoE with esophageal squamous cell carcinoma induced by the carcinogen 4-nitroquinoline 1-oxide (4NQO). 10/10 mice treated with 4NQOalone developed ESCC as expected in this robust carcinogen-driven tumor model. In mice co-treated with MC903/OVA and 4NQO, esophageal tumors were detected in 4/5 mice with a significant decrease in tumor load as compared to mice treated with 4NQO alone. Notably, 6/6 mice treated withMC903/OVA alone and 4/4 mice treated with propylene glycol (vehicle for 4NQO) failed to display tumors. To examine the possibility that EoE may induce an anti-tumor inflammatory milieu, we exposed primary esophageal tumor cells to CD45positive immune cells isolated from the peripheral blood of strain- matched donor mice with or without food allergen-mediated EoE. These experiments revealed a robust induction of apoptotic cell death in tumor cells exposed to immune cells from EoE donor mice as compared to those exposed to immune cells from naive controls. Finally, in order to investigate how EoE and cancer may differentially impact esophageal biology, single cell RNA-sequencing was performed and further identified differences in the esophageal epithelial and immune cell compartments in mice with EoE as compared to those with cancer. The innovative approaches employed here, including combining mouse models of EoE and esophageal cancer capability, establish a robust experimental platform to define the relationship between EoE and esophageal cancer which will be further used for future functional investigations to define the precise cellular and molecular mechanisms through which EoE inflammation limits carcinogenesis. As allergic disorders promote systemic inflammation, findings from the current study may be applicable to cancers occurring in organs other than the esophagus. Citation Format: Mohammad Faujul Kabir, Adam Karami, Anbin Mu, Kelly A. Whelan. Exploring the relation of eosinophilic esophagitis (EoE) with esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1752.