Role of the IL-33/ST2L axis in colorectal cancer progression

Abstract

Interleukin-33 (IL-33) has been identified as a natural ligand of ST2L. IL-33 primarily acts as a key regulator of Th2 responses through binding to ST2L, which is antagonized by soluble ST2 (sST2). The IL-33/ST2L axis is involved in various inflammatory pathologies, including ulcerative colitis (UC). Several recent investigations have also suggested that the IL-33/ST2L axis plays a role in colorectal cancer (CRC) progression. In CRC, tumor- and stroma-derived IL-33 may activate ST2L on various cell types in an autocrine and paracrine manner. Although several findings support the hypothesis that the IL-33/ST2L axis positively regulates CRC progression, other reports do not; hence, this hypothesis remains controversial. At any rate, recent studies have provided overwhelming evidence that the IL-33/ST2L axis plays important roles in CRC progression. This review summarizes the role of the IL-33/ST2L axis in the UC and CRC microenvironments.

Keywords: Colorectal cancer; Inflammatory tumor microenvironment; Interleukin-33; ST2L; Ulcerative colitis; sST2.