Giannou, Anastasios D;
Lücke, Jöran;
Kleinschmidt, Dörte;
Shiri, Ahmad Mustafa;
Steglich, Babett;
Nawrocki, Mikolaj;
Zhang, Tao;
... Huber, Samuel; + view all
(2022)
A Critical Role of the IL-22-IL-22 Binding Protein Axis in Hepatocellular Carcinoma.
Cancers (Basel)
, 14
(24)
, Article 6019. 10.3390/cancers14246019.
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Abstract
Hepatocellular carcinoma (HCC) ranks among the five most common cancer entities worldwide and leads to hundred-thousands of deaths every year. Despite some groundbreaking therapeutical revelations during the last years, the overall prognosis remains poor. Although the immune system fights malignant transformations with a robust anti-tumor response, certain immune mediators have also been shown to promote cancer development. For example, interleukin (IL)-22 has been associated with HCC progression and worsened prognosis in multiple studies. However, the underlying mechanisms of the pathological role of IL-22-signaling as well as the role of its natural antagonist IL-22 binding protein (IL-22BP) in HCC remain elusive. Here, we corroborate the pathogenic role of IL-22 in HCC by taking advantage of two mouse models. Moreover, we observed a protective role of IL-22BP during liver carcinogenesis. While IL-22 was mainly produced by CD4+ T cells in HCC, IL-22BP was abundantly expressed by neutrophils during liver carcinogenesis. Hepatocytes could be identified as a major target of this pathological IL-22-signaling. Moreover, abrogation of IL-22 signaling in hepatocytes in IL22ra1flox/flox × AlbCre+ mice reduced STEAP4 expression-a known oncogene-in HCC in vivo. Likewise, STEAP4 expression correlated with IL22 levels in human HCC samples, but not in healthy liver specimens. In conclusion, these data encourage the development of therapeutical approaches that target the IL-22-IL-22BP axis in HCC.
| Type: | Article |
|---|---|
| Title: | A Critical Role of the IL-22-IL-22 Binding Protein Axis in Hepatocellular Carcinoma |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/cancers14246019 |
| Publisher version: | https://doi.org/10.3390/cancers14246019 |
| Language: | English |
| Additional information: | © 2022 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://creativecommons.org/licenses/by/4.0/). |
| Keywords: | IL-22, IL-22BP, Th22, hepatocellular carcinoma, neutrophils |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10162377 |
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