The Importance of Th2 Immune Responses in Mediating the Progression of Gastritis-Associated Metaplasia to Gastric Cancer

Simple Summary Gastric cancer is one of the most prevalent and deadliest neoplasms worldwide. Although significant advances have been made in recent decades to improve its treatment, an incomplete understanding of its etiology and pathogenesis still limits our ability to effectively prevent and treat gastric cancer. It is well established that the most common subtype of gastric cancer (intestinal gastric cancer) develops through a multi-step process, wherein pathologic changes in gastric cells progressively occur, ultimately leading to the development of tumors. Recent evidence suggests that, aside from environmental factors, the immune system plays a key role in the sequela from gastritis to metaplasia, dysplasia and finally, gastric cancer, primarily through type 2 immune responses. In this review, we summarize the current literature and provide an overall interpretation regarding the impact of T helper 2 (Th2) immunity on the development and progression of gastric cancer.Abstract Gastric cancer is one of the leading causes of cancer deaths worldwide, with chronic gastritis representing the main predisposing factor initiating the cascade of events leading to metaplasia and eventually progressing to cancer. A widely accepted classification distinguishes between autoimmune and environmental atrophic gastritis, mediated, respectively, by T cells promoting the destruction of the oxyntic mucosa, and chronic H. pylori infection, which has also been identified as the major risk factor for gastric cancer. The original dogma posits Th1 immunity as a main causal factor for developing gastritis and metaplasia. Recently, however, it has become evident that Th2 immune responses play a major role in the events causing chronic inflammation leading to tumorigenesis, and in this context, many different cell types and cytokines are involved. In particular, the activity of cytokines, such as IL-33 and IL-13, and cell types, such as mast cells, M2 macrophages and eosinophils, are intertwined in the process, promoting chronic gastritis-dependent and more diffuse metaplasia. Herein, we provide an overview of the critical events driving the pathology of this disease, focusing on the most recent findings regarding the importance of Th2 immunity in gastritis and gastric metaplasia.