Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight.

Valentina La Sorsa,Gilda Varricchi,Jacopo Mancini,Simone Marcella,Stefania Loffredo,Giovanna Schiavoni,Fabrizio Mattei,Sara Andreone,Adriana Rosa Gambardella

doi:10.3389/fimmu.2020.571593

Abstract

Interleukin-33 (IL-33) is an epithelial-derived cytokine that can be released upon tissue damage, stress, or infection, acting as an alarmin for the immune system. IL-33 has long been studied in the context of Th2-related immunopathologies, such as allergic diseases and parasitic infections. However, its capacity to stimulate also Th1-type of immune responses is now well established. IL-33 binds to its specific receptor ST2 expressed by most immune cell populations, modulating a variety of responses. In cancer immunity, IL-33 can display both pro-tumoral and anti-tumoral functions, depending on the specific microenvironment. Recent findings indicate that IL-33 can effectively stimulate immune effector cells (NK and CD8+ T cells), eosinophils, basophils and type 2 innate lymphoid cells (ILC2) promoting direct and indirect anti-tumoral activities. In this review, we summarize the most recent advances on anti-tumor immune mechanisms operated by IL-33, including the modulation of immune checkpoint molecules, with the aim to understand its potential as a therapeutic target in cancer.

Highlights

Interleukin-33 (IL-33) was initially described by JP Girard’s group as a nuclear factor from high endothelial venules (NF-HEV) [1]
The role of IL-33 in cancer immunity remains controversial, it appears that this alarmin has beneficial effects in certain types of experimental tumors, melanoma [16, 20,21,22, 31, 51, 57]
The current literature suggests that the anti-tumor properties of IL-33 are attributable to its capacity to stimulate CD8+ T cells, NK, dendritic cells (DC), eosinophils and type 2 innate lymphoid cells (ILC2) (Figure 1)

Summary

Introduction

Interleukin-33 (IL-33) was initially described by JP Girard’s group as a nuclear factor from high endothelial venules (NF-HEV) [1]. The IL-33/ST2 axis has a controversial role in cancer immunity, since both pro- and anti-tumoral functions have been reported. Transgenic expression of IL-33 in B16 or 4T1 tumor cells [20] or in the host [21], as well as exogenous administration of the recombinant protein [22] induce the recruitment of activated (IFN-g+ CD107+) CD8+ T and NK cells in the TME, which inhibited tumor growth in mice.

Results

Conclusion