The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape
Interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays a critical role in maintaining tissue homeostasis as well as pathological conditions, such as allergy, infectious disease, and cancer, by promoting type 1 and 2 immune responses. Through its specific receptor ST2, IL-33 exerts multi...
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doaj-2d6afd5fc78e401e92805eb8f6eba17f2021-07-15T15:31:51ZengMDPI AGCancers2072-66942021-06-01133281328110.3390/cancers13133281The Janus Face of IL-33 Signaling in Tumor Development and Immune EscapeMi-Ran Choi0Jeffrey A. Sosman1Bin Zhang2Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USARobert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USARobert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USAInterleukin-33 (IL-33), a member of the IL-1 cytokine family, plays a critical role in maintaining tissue homeostasis as well as pathological conditions, such as allergy, infectious disease, and cancer, by promoting type 1 and 2 immune responses. Through its specific receptor ST2, IL-33 exerts multifaceted functions through the activation of diverse intracellular signaling pathways. ST2 is expressed in different types of immune cells, including Th2 cells, Th1 cells, CD8<sup>+</sup> T cells, regulatory T cells (T<sub>reg</sub>), cytotoxic NK cells, group 2 innate lymphoid cells (ILC2s), and myeloid cells. During cancer initiation and progression, the aberrant regulation of the IL-33/ST2 axis in the tumor microenvironment (TME) extrinsically and intrinsically mediates immune editing via modulation of both innate and adaptive immune cell components. The summarized results in this review suggest that IL-33 exerts dual-functioning, pro- as well as anti-tumorigenic effects depending on the tumor type, expression levels, cellular context, and cytokine milieu. A better understanding of the distinct roles of IL-33 in epithelial, stromal, and immune cell compartments will benefit the development of a targeting strategy for this IL-33/ST2 axis for cancer immunotherapy.https://www.mdpi.com/2072-6694/13/13/3281IL-33ST2immune editingcellular contextcancer immunotherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mi-Ran Choi Jeffrey A. Sosman Bin Zhang |
spellingShingle |
Mi-Ran Choi Jeffrey A. Sosman Bin Zhang The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape Cancers IL-33 ST2 immune editing cellular context cancer immunotherapy |
author_facet |
Mi-Ran Choi Jeffrey A. Sosman Bin Zhang |
author_sort |
Mi-Ran Choi |
title |
The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape |
title_short |
The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape |
title_full |
The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape |
title_fullStr |
The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape |
title_full_unstemmed |
The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape |
title_sort |
janus face of il-33 signaling in tumor development and immune escape |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-06-01 |
description |
Interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays a critical role in maintaining tissue homeostasis as well as pathological conditions, such as allergy, infectious disease, and cancer, by promoting type 1 and 2 immune responses. Through its specific receptor ST2, IL-33 exerts multifaceted functions through the activation of diverse intracellular signaling pathways. ST2 is expressed in different types of immune cells, including Th2 cells, Th1 cells, CD8<sup>+</sup> T cells, regulatory T cells (T<sub>reg</sub>), cytotoxic NK cells, group 2 innate lymphoid cells (ILC2s), and myeloid cells. During cancer initiation and progression, the aberrant regulation of the IL-33/ST2 axis in the tumor microenvironment (TME) extrinsically and intrinsically mediates immune editing via modulation of both innate and adaptive immune cell components. The summarized results in this review suggest that IL-33 exerts dual-functioning, pro- as well as anti-tumorigenic effects depending on the tumor type, expression levels, cellular context, and cytokine milieu. A better understanding of the distinct roles of IL-33 in epithelial, stromal, and immune cell compartments will benefit the development of a targeting strategy for this IL-33/ST2 axis for cancer immunotherapy. |
topic |
IL-33 ST2 immune editing cellular context cancer immunotherapy |
url |
https://www.mdpi.com/2072-6694/13/13/3281 |
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