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IL‐33/ST2 as a potential target for tumor immunotherapy
Author(s) -
Jiang Wenyi,
Lian Jingyao,
Yue Ying,
Zhang Yi
Publication year - 2021
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.202149175
Subject(s) - immune system , biology , tumor microenvironment , immunotherapy , cancer immunotherapy , cancer research , inflammation , regulator , immunology , cytokine , microbiology and biotechnology , biochemistry , gene
Abstract IL‐33, a member of the IL‐1 family, was initially reported to be expressed constitutively in the nucleus of tissue‐lining and structural cells. However, upon tissue damage or injury, IL‐33 can be released quickly to bind with its cognate receptor ST2 in response to wound healing and inflammation and act as a DAMP. As a key regulator of Th2 responses, IL‐33/ST2 signal is primarily associated with immunity and immune‐related disorders. In recent years, IL‐33/ST2 signaling pathway has been reported to promote the development of cancer and remodel the tumor microenvironment by expanding immune suppressive cells such as myeloid‐derived suppressor cells or regulatory T cells. However, its role remains controversial in some tumor settings. IL‐33 could also promote effective infiltration of immune cells such as CD8 + T and NK cells, which act as antitumor. These dual effects may limit the clinical application to target this cytokine axis. Therefore, more comprehensive exploration and deeper understanding of IL‐33 are required. In this review, we summarized the IL‐33/ST2 axis versatile roles in the tumor microenvironment with a focus on the IL‐33‐target immune cells and downstream signaling pathways. We also discuss how the IL‐33/ST2 axis could be used as a potential therapeutic target for cancer immunotherapy.