Decoding the IL-33/ST2 Axis: Its Impact on the Immune Landscape of Breast Cancer

Sep 24, 2026

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Interleukin-33 (IL-33) is presented as a key cytokine shaping immune regulation, with emphasized relevance to cancer. The review details how the IL-33/ST2 axis influences breast cancer biology, including cancer cell proliferation and differentiation, modulation of the tumor microenvironment, and effects on cancer metabolism. It links this signaling pathway to tumor progression, metastasis, and resistance to conventional therapies. Therapeutic potential is discussed through targeting IL-33/ST2 in cancer immunotherapy and as an adjuvant to immune checkpoint blockade, while noting controversy due to opposing pro- and anti-tumor effects.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

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Abstract

Introduction

Breast cancer burden and need for improved management

Metastasis as the main driver of mortality

Heterogeneity and molecular subtypes

IL-33 biology and relevance to cancer

Review Decoding the IL-33/ST2 Axis: Its Impact on the Immune Landscape of Breast Cancer Bojan Stojanovic 1,†, Nevena Gajovic 2,†, Milena Jurisevic 3, Milica Dimitrijevic Stojanovic 2,4,*, Marina Jovanovic 5, Ivan Jovanovic 2, Bojana S. Stojanovic 2,6,* and Bojan Milosevic 1 Citation: Stojanovic, B.; Gajovic, N.; Jurisevic, M.; Stojanovic, M.D.; Jovanovic, M.; Jovanovic, I.; Stojanovic, B.S.; Milosevic, B. Decoding the IL-33/ST2 Axis: Its Impact on the Immune Landscape of Breast Cancer. Int. J. Mol. Sci. 2023, 24, 14026. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms241814026](10.3390/ijms241814026) Academic Editor: Yasuhiro Miki 1 Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia; [bojan.stojanovic01@gmail.com](bojan.stojanovic01@gmail.com) (B.S.) 2 Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia; [ivanjovanovic77@gmail.com](ivanjovanovic77@gmail.com) (I.J.) 3 Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia; [milena.jurisevic13@gmail.com](milena.jurisevic13@gmail.com) 4 Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia 5 Department of Otorinolaringology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia 6 Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia * [Correspondence: milicadimitrijevic@yahoo.om](Correspondence: milicadimitrijevic@yahoo.om) (M.D.S.); [bojana.stojanovic04@gmail.com](bojana.stojanovic04@gmail.com) (B.S.S.)† These authors contributed equally to this work. Abstract: Interleukin-33 (IL-33) has emerged as a critical cytokine in the regulation of the immune system, showing a pivotal role in the pathogenesis of various diseases including cancer. This review emphasizes the role of the IL-33/ST2 axis in breast cancer biology, its contribution to cancer progression and metastasis, its inﬂuence on the tumor microenvironment and cancer metabolism, and its potential as a therapeutic target. The IL-33/ST2 axis has been shown to have extensive pro-tumorigenic features in breast cancer, starting from tumor tissue proliferation and differentiation to modulating both cancer cells and anti-tumor immune response. It has also been linked to the resistance of cancer cells to conventional therapeutics. However, the role of IL-33 in cancer therapy remains controversial due to the conﬂicting effects of IL-33 in tumorigenesis and anti-tumor response. The possibility of targeting the IL-33/ST2 axis in tumor immunotherapy, or as an adjuvant in immune checkpoint blockade therapy, is discussed. Keywords: Interleukin-33; breast cancer; tumor microenvironment; immunotherapy; metastasis 1. Introduction Received: 10 August 2023 Revised: 1 September 2023 Accepted: 7 September 2023 Published: 13 September 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Breast cancer, characterized by an uncontrolled proliferation of mammary gland cells, is the most frequently diagnosed malignancy in women globally [1] . With an estimated 2.2 million cases and approximately 700,000 fatalities in 2021, there is an indisputable urgency to advance early detection techniques, innovate therapeutic interventions, and extend the realm of research [1] . These alarming statistics underscore the profound need for progress towards the effective management and, ultimately, the eradication of this substantial global health burden. Comprising approximately 14

FAQs

What biological processes does the IL-33/ST2 axis affect in breast cancer?

The review emphasizes effects on cancer progression and metastasis, including tumor cell proliferation and differentiation, modulation of the tumor microenvironment, and impacts on cancer metabolism.

How is IL-33 linked to treatment resistance in breast cancer?

The IL-33/ST2 axis is reported as being associated with resistance of cancer cells to conventional therapeutics.

Why is targeting IL-33/ST2 considered controversial in cancer therapy?

Because IL-33 is described as having conflicting effects across tumorigenesis and anti-tumor immune responses, the therapeutic role in cancer treatment remains debated.

Sep 24, 2026

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