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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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Autores principales: Zhang, Tao, Wahib, Ramez, Zazara, Dimitra E., Lücke, Jöran, Shiri, Ahmad Mustafa, Kempski, Jan, Zhao, Lilan, Agalioti, Theodora, Machicote, Andres Pablo, Giannou, Olympia, Belios, Ioannis, Jia, Rongrong, Zhang, Siwen, Tintelnot, Joseph, Seese, Hannes, Grass, Julia Kristin, Mercanoglu, Baris, Stern, Louisa, Scognamiglio, Pasquale, Fard-Aghaie, Mohammad, Seeger, Philipp, Wakker, Jonas, Kemper, Marius, Brunswig, Benjamin, Duprée, Anna, Lykoudis, Panagis M., Pikouli, Anastasia, Giorgakis, Emmanouil, Stringa, Pablo, Lausada, Natalia, Gentilini, Maria Virginia, Gondolesi, Gabriel E., Bachmann, Kai, Busch, Philipp, Grotelüschen, Rainer, Maroulis, Ioannis C., Arck, Petra C., Nakano, Ryosuke, Thomson, Angus W., Ghadban, Tarik, Tachezy, Michael, Melling, Nathaniel, Achilles, Eike-Gert, Puelles, Victor G., Nickel, Felix, Hackert, Thilo, Mann, Oliver, Izbicki, Jakob R., Li, Jun, Gagliani, Nicola, Huber, Samuel, Giannou, Anastasios D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591777/
https://www.ncbi.nlm.nih.gov/pubmed/37876835
http://dx.doi.org/10.1080/2162402X.2023.2269634
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author Zhang, Tao
Wahib, Ramez
Zazara, Dimitra E.
Lücke, Jöran
Shiri, Ahmad Mustafa
Kempski, Jan
Zhao, Lilan
Agalioti, Theodora
Machicote, Andres Pablo
Giannou, Olympia
Belios, Ioannis
Jia, Rongrong
Zhang, Siwen
Tintelnot, Joseph
Seese, Hannes
Grass, Julia Kristin
Mercanoglu, Baris
Stern, Louisa
Scognamiglio, Pasquale
Fard-Aghaie, Mohammad
Seeger, Philipp
Wakker, Jonas
Kemper, Marius
Brunswig, Benjamin
Duprée, Anna
Lykoudis, Panagis M.
Pikouli, Anastasia
Giorgakis, Emmanouil
Stringa, Pablo
Lausada, Natalia
Gentilini, Maria Virginia
Gondolesi, Gabriel E.
Bachmann, Kai
Busch, Philipp
Grotelüschen, Rainer
Maroulis, Ioannis C.
Arck, Petra C.
Nakano, Ryosuke
Thomson, Angus W.
Ghadban, Tarik
Tachezy, Michael
Melling, Nathaniel
Achilles, Eike-Gert
Puelles, Victor G.
Nickel, Felix
Hackert, Thilo
Mann, Oliver
Izbicki, Jakob R.
Li, Jun
Gagliani, Nicola
Huber, Samuel
Giannou, Anastasios D.
author_facet Zhang, Tao
Wahib, Ramez
Zazara, Dimitra E.
Lücke, Jöran
Shiri, Ahmad Mustafa
Kempski, Jan
Zhao, Lilan
Agalioti, Theodora
Machicote, Andres Pablo
Giannou, Olympia
Belios, Ioannis
Jia, Rongrong
Zhang, Siwen
Tintelnot, Joseph
Seese, Hannes
Grass, Julia Kristin
Mercanoglu, Baris
Stern, Louisa
Scognamiglio, Pasquale
Fard-Aghaie, Mohammad
Seeger, Philipp
Wakker, Jonas
Kemper, Marius
Brunswig, Benjamin
Duprée, Anna
Lykoudis, Panagis M.
Pikouli, Anastasia
Giorgakis, Emmanouil
Stringa, Pablo
Lausada, Natalia
Gentilini, Maria Virginia
Gondolesi, Gabriel E.
Bachmann, Kai
Busch, Philipp
Grotelüschen, Rainer
Maroulis, Ioannis C.
Arck, Petra C.
Nakano, Ryosuke
Thomson, Angus W.
Ghadban, Tarik
Tachezy, Michael
Melling, Nathaniel
Achilles, Eike-Gert
Puelles, Victor G.
Nickel, Felix
Hackert, Thilo
Mann, Oliver
Izbicki, Jakob R.
Li, Jun
Gagliani, Nicola
Huber, Samuel
Giannou, Anastasios D.
author_sort Zhang, Tao
collection PubMed
description 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.
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spelling pubmed-105917772023-10-24 CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis Zhang, Tao Wahib, Ramez Zazara, Dimitra E. Lücke, Jöran Shiri, Ahmad Mustafa Kempski, Jan Zhao, Lilan Agalioti, Theodora Machicote, Andres Pablo Giannou, Olympia Belios, Ioannis Jia, Rongrong Zhang, Siwen Tintelnot, Joseph Seese, Hannes Grass, Julia Kristin Mercanoglu, Baris Stern, Louisa Scognamiglio, Pasquale Fard-Aghaie, Mohammad Seeger, Philipp Wakker, Jonas Kemper, Marius Brunswig, Benjamin Duprée, Anna Lykoudis, Panagis M. Pikouli, Anastasia Giorgakis, Emmanouil Stringa, Pablo Lausada, Natalia Gentilini, Maria Virginia Gondolesi, Gabriel E. Bachmann, Kai Busch, Philipp Grotelüschen, Rainer Maroulis, Ioannis C. Arck, Petra C. Nakano, Ryosuke Thomson, Angus W. Ghadban, Tarik Tachezy, Michael Melling, Nathaniel Achilles, Eike-Gert Puelles, Victor G. Nickel, Felix Hackert, Thilo Mann, Oliver Izbicki, Jakob R. Li, Jun Gagliani, Nicola Huber, Samuel Giannou, Anastasios D. Oncoimmunology Original Research 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. Taylor & Francis 2023-10-20 /pmc/articles/PMC10591777/ /pubmed/37876835 http://dx.doi.org/10.1080/2162402X.2023.2269634 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Original Research
Zhang, Tao
Wahib, Ramez
Zazara, Dimitra E.
Lücke, Jöran
Shiri, Ahmad Mustafa
Kempski, Jan
Zhao, Lilan
Agalioti, Theodora
Machicote, Andres Pablo
Giannou, Olympia
Belios, Ioannis
Jia, Rongrong
Zhang, Siwen
Tintelnot, Joseph
Seese, Hannes
Grass, Julia Kristin
Mercanoglu, Baris
Stern, Louisa
Scognamiglio, Pasquale
Fard-Aghaie, Mohammad
Seeger, Philipp
Wakker, Jonas
Kemper, Marius
Brunswig, Benjamin
Duprée, Anna
Lykoudis, Panagis M.
Pikouli, Anastasia
Giorgakis, Emmanouil
Stringa, Pablo
Lausada, Natalia
Gentilini, Maria Virginia
Gondolesi, Gabriel E.
Bachmann, Kai
Busch, Philipp
Grotelüschen, Rainer
Maroulis, Ioannis C.
Arck, Petra C.
Nakano, Ryosuke
Thomson, Angus W.
Ghadban, Tarik
Tachezy, Michael
Melling, Nathaniel
Achilles, Eike-Gert
Puelles, Victor G.
Nickel, Felix
Hackert, Thilo
Mann, Oliver
Izbicki, Jakob R.
Li, Jun
Gagliani, Nicola
Huber, Samuel
Giannou, Anastasios D.
CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
title CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
title_full CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
title_fullStr CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
title_full_unstemmed CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
title_short CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
title_sort cd4+ t cell-derived il-22 enhances liver metastasis by promoting angiogenesis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591777/
https://www.ncbi.nlm.nih.gov/pubmed/37876835
http://dx.doi.org/10.1080/2162402X.2023.2269634
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