Interleukin-33 and ST2 Signaling in Tumor Microenvironment

Interleukin-33 (IL-33) is one of the members of the IL-1 family of cytokines and a ligand of ST2 and IL-1 receptor accessory protein (IL-1RAcP) that is known to affect Th2 inflammatory response with partial effects on Th1 responses. This cytokine is released by epithelial and smooth muscle cells of the airway system during their injury by several environmental stimuli, such as allergens, viruses, helminths, and pollutants. IL-33 is an alarmin that acts as an endogenous danger signal, and it has been known to affect various types of cells, such as mast cells, basophils, eosinophils, T cells, and specific subsets of innate lymphoid cells (ILCs). In recent findings, this cytokine is believed to have a critical role in several types of cancers, such as lung cancer, liver cancer, and head and neck squamous cell cancer. The expression of IL-33/ST2 in cancer tissues shows a close association with tumor growth and tumor progression in several types of cancer, suggesting the IL-33/ST2 pathway as a potential target for therapy.