ST2 Signaling in the Tumor Microenvironment

Chih Peng Chang, Meng Hsuan Hu, Yu Peng Hsiao, Yi Ching Wang

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Suppression of tumorigenicity 2 (ST2), also known as interleukin-1 receptor-like 1 (IL1RL1), is one of the natural receptors of IL-33. Three major isoforms, ST2L (transmembrane form), sST2 (soluble form), and ST2V, are generated by alternative splicing. Damage to stromal cells induces necrosis and release of IL-33, which binds to heterodimeric ST2L/IL-1RAcP complex on the membrane of a variety of immune cells. This IL-33/ST2L signal induces transcription of the downstream inflammatory and anti-inflammatory genes by activating diverse intracellular kinases and factors to mount an adequate immune response, even in tumor microenvironment. For example, activation of IL-33/ST2L signal may trigger Th2-dependent M2 macrophage polarization to facilitate tumor progression. Notably, sST2 is a soluble form of ST2 that lacks a transmembrane domain but preserves an extracellular domain similar to ST2L, which acts as a “decoy” receptor for IL-33. sST2 has been shown to involve in the inflammatory tumor microenvironment and the progression of colorectal cancer, non-small cell lung cancer, and gastric cancer. Therefore, targeting the IL-33/ST2 axis becomes a promising new immunotherapy for treatment of many cancers. This chapter reviews the recent findings on IL-33/ST2L signaling in tumor microenvironment, the trafficking mode of sST2, and the pharmacological strategies to target IL-33/ST2 axis for cancer treatment.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages83-93
Number of pages11
DOIs
Publication statusPublished - 2020 Jan 1

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1240
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Chang, C. P., Hu, M. H., Hsiao, Y. P., & Wang, Y. C. (2020). ST2 Signaling in the Tumor Microenvironment. In Advances in Experimental Medicine and Biology (pp. 83-93). (Advances in Experimental Medicine and Biology; Vol. 1240). Springer. https://doi.org/10.1007/978-3-030-38315-2_7