A Tale of Two Stromal Components: Influence of Fibroblasts, Innate Lymphoid Cells Type 2, and Interleukin 13 in Stomach Metaplasia

Abstract

A TALE OF TWO STROMAL COMPONENTS: INFLUENCE OF FIBROBLASTS, INNATE LYMPHOID CELLS TYPE 2, AND INTERLEUKIN 13 IN STOMACH METAPLASIA

Gastric cancer is one of the leading causes of cancer mortality worldwide, however, key regulators and mechanisms involved in gastric carcinogenesis remain unclear. The onset of metaplasia phenotypes in the stomach is correlated with the development of gastric cancer. Therefore, understanding the cellular events that lead to stomach metaplasia maturation and progression remains a priority. Studies from our group have demonstrated that immune components are key regulators for the development of metaplasia in the stomach. Moreover, increasing evidence suggests that fibroblasts can be responsible for the progression of pre-neoplastic lineages in different types of epithelial-type cancers. The first part of my studies shows the establishment and characterization of a novel organoid model for the study of Spasmolytic Polypeptide-Expressing Metaplasia (SPEM) cells and demonstrates the role of Group 2 innate lymphoid cells (ILC2s) and Interleukin 13 (IL-13) in their maturation and proliferation. The second part of my studies shows the characterization of fibroblast populations across different stages of the stomach cancer carcinogenesis process and demonstrates the influence of metaplasia- and cancer-derived fibroblasts in metaplasia progression toward dysplasia.