TNF+ regulatory T cells regulate the stemness of gastric cancer cells through the IL13/STAT3 pathway

Abstract

Regulatory T cells (Tregs) are an important component of the tumor microenvironment; however, the interaction between Tregs and gastric cancer cells is not completely understood. Recent studies have shown that Tregs participate in cancer cell stemness maintenance. In this study, we performed single-cell RNA sequencing of gastric cancer and adjacent tissues and found that Tregs with high TNF expression were recruited to gastric cancer tissues and were significantly correlated with patient survival. TNF+ Tregs significantly contribute to tumor growth and progression. Our studies have further demonstrated that TNF+ Tregs promote the stemness of gastric cancer cells through the IL13/STAT3 pathway. Therefore, blocking the interaction between TNF+ Tregs and gastric cancer cells may be a new approach in the treatment of gastric cancer.

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

“…In line with these findings, a recent study identifying AQP5 in SPEM glands and at the base of incomplete intestinal metaplasia glands demonstrates that AQP5 expression is under the control of IL-13, further reinforcing the concept that this cytokine plays a fundamental role in the development of metaplasia and possibly, its progression to cancer [64]. Another recent study identified TNF + Tregs as a source of IL-13 and proposes that IL-13 promotes self-renewal, migration and colony formation of gastric cancer cells via the phosphorylation of STAT3 [100].…”