CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis

Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is o...

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Main Authors: Tao Zhang, Ramez Wahib, Dimitra E. Zazara, Jöran Lücke, Ahmad Mustafa Shiri, Jan Kempski, Lilan Zhao, Theodora Agalioti, Andres Pablo Machicote, Olympia Giannou, Ioannis Belios, Rongrong Jia, Siwen Zhang, Joseph Tintelnot, Hannes Seese, Julia Kristin Grass, Baris Mercanoglu, Louisa Stern, Pasquale Scognamiglio, Mohammad Fard-Aghaie, Philipp Seeger, Jonas Wakker, Marius Kemper, Benjamin Brunswig, Anna Duprée, Panagis M. Lykoudis, Anastasia Pikouli, Emmanouil Giorgakis, Pablo Stringa, Natalia Lausada, Maria Virginia Gentilini, Gabriel E. Gondolesi, Kai Bachmann, Philipp Busch, Rainer Grotelüschen, Ioannis C. Maroulis, Petra C. Arck, Ryosuke Nakano, Angus W. Thomson, Tarik Ghadban, Michael Tachezy, Nathaniel Melling, Eike-Gert Achilles, Victor G. Puelles, Felix Nickel, Thilo Hackert, Oliver Mann, Jakob R. Izbicki, Jun Li, Nicola Gagliani, Samuel Huber, Anastasios D. Giannou
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:OncoImmunology
Subjects:
IL-22
liver metastasis
Th22
Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2023.2269634
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Summary:Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.
ISSN:2162-402X

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