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Int J Mol Sci. 2018 Sep 9;19(9). pii: E2676. doi: 10.3390/ijms19092676.

The Role of IL-33/ST2 Pathway in Tumorigenesis.

Author information

1
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA. kmlarsen@email.sc.edu.
2
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA. maydelis_minaya@brown.edu.
3
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA. vivekvaish@live.com.
4
Department of Biological Sciences and Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208, USA. mpena@biol.sc.edu.

Abstract

Cancer is initiated by mutations in critical regulatory genes; however, its progression to malignancy is aided by non-neoplastic cells and molecules that create a permissive environment known as the tumor stroma or microenvironment (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a nuclear factor. IL-33 typically resides in the nucleus of the cells where it is expressed. However, upon tissue damage, necrosis, or injury, it is quickly released into extracellular space where it binds to its cognate receptor suppression of tumorigenicity 2 (ST2)L found on the membrane of target cells to potently activate a T Helper 2 (Th2) immune response, thus, it is classified as an alarmin. While its role in immunity and immune-related disorders has been extensively studied, its role in tumorigenesis is only beginning to be elucidated and has revealed opposing roles in tumor development. The IL-33/ST2 axis is emerging as a potent modulator of the TME. By recruiting a cohort of immune cells, it can remodel the TME to promote malignancy or impose tumor regression. Here, we review its multiple functions in various cancers to better understand its potential as a therapeutic target to block tumor progression or as adjuvant therapy to enhance the efficacy of anticancer immunotherapies.

KEYWORDS:

IL-33/ST2 signaling; Interleukin 33; cancer; inflammation; tumor microenvironment

PMID:
30205617
PMCID:
PMC6164146
DOI:
10.3390/ijms19092676
[Indexed for MEDLINE]
Free PMC Article

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