CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
ABSTRACTMetastasis 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 netw...
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2269634 |
| _version_ | 1797367110780846080 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Tao Zhang |
| collection | DOAJ |
| description | ABSTRACTMetastasis 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. |
| first_indexed | 2024-03-08T17:12:40Z |
| format | Article |
| id | doaj.art-3cee1dcf7a0d46038cb4bbb3cfb81bcf |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-03-08T17:12:40Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-3cee1dcf7a0d46038cb4bbb3cfb81bcf2024-01-03T19:25:36ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2269634CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesisTao Zhang0Ramez Wahib1Dimitra E. Zazara2Jöran Lücke3Ahmad Mustafa Shiri4Jan Kempski5Lilan Zhao6Theodora Agalioti7Andres Pablo Machicote8Olympia Giannou9Ioannis Belios10Rongrong Jia11Siwen Zhang12Joseph Tintelnot13Hannes Seese14Julia Kristin Grass15Baris Mercanoglu16Louisa Stern17Pasquale Scognamiglio18Mohammad Fard-Aghaie19Philipp Seeger20Jonas Wakker21Marius Kemper22Benjamin Brunswig23Anna Duprée24Panagis M. Lykoudis25Anastasia Pikouli26Emmanouil Giorgakis27Pablo Stringa28Natalia Lausada29Maria Virginia Gentilini30Gabriel E. Gondolesi31Kai Bachmann32Philipp Busch33Rainer Grotelüschen34Ioannis C. Maroulis35Petra C. Arck36Ryosuke Nakano37Angus W. Thomson38Tarik Ghadban39Michael Tachezy40Nathaniel Melling41Eike-Gert Achilles42Victor G. Puelles43Felix Nickel44Thilo Hackert45Oliver Mann46Jakob R. Izbicki47Jun Li48Nicola Gagliani49Samuel Huber50Anastasios D. Giannou51Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDivision for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyComputer Engineering & Informatics Dept, University of Patras, Patras, GreeceDivision for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany3rd Department of Surgery, National & Kapodistrian University of Athens, Athens, Greece3rd Department of Surgery, National & Kapodistrian University of Athens, Athens, GreeceWinthrop P Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USADepartment General Surgery, Liver, Pancreas and Intestinal Transplantation, Hospital Universitario, Fundacion Favaloro, Buenos Aires, ArgentinaDepartment General Surgery, Liver, Pancreas and Intestinal Transplantation, Hospital Universitario, Fundacion Favaloro, Buenos Aires, ArgentinaInstituto de Medicina Traslacional, Trasplante y Bioingeniería (IMETTyB, CONICET, Universidad Favaloro), Laboratorio de Inmunología asociada al Trasplante, Buenos Aires, ArgentinaDepartment General Surgery, Liver, Pancreas and Intestinal Transplantation, Hospital Universitario, Fundacion Favaloro, Buenos Aires, ArgentinaDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Surgery, University of Patras Medical School, Patras, GreeceDivision for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Surgery, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Surgery, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyIII. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyABSTRACTMetastasis 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.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2269634IL-22liver metastasisTh22 |
| spellingShingle | 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 CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis OncoImmunology IL-22 liver metastasis Th22 |
| 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 | IL-22 liver metastasis Th22 |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2269634 |
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