OncoImmunology (Dec 2023)
CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
- 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
Affiliations
- Tao Zhang
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Ramez Wahib
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Dimitra E. Zazara
- Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Jöran Lücke
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Ahmad Mustafa Shiri
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Jan Kempski
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Lilan Zhao
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Theodora Agalioti
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Andres Pablo Machicote
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Olympia Giannou
- Computer Engineering & Informatics Dept, University of Patras, Patras, Greece
- Ioannis Belios
- Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Rongrong Jia
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Siwen Zhang
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Joseph Tintelnot
- Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hannes Seese
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Julia Kristin Grass
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Baris Mercanoglu
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Louisa Stern
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Pasquale Scognamiglio
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Mohammad Fard-Aghaie
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Philipp Seeger
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Jonas Wakker
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Marius Kemper
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Benjamin Brunswig
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Anna Duprée
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Panagis M. Lykoudis
- 3rd Department of Surgery, National & Kapodistrian University of Athens, Athens, Greece
- Anastasia Pikouli
- 3rd Department of Surgery, National & Kapodistrian University of Athens, Athens, Greece
- Emmanouil Giorgakis
- Winthrop P Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Pablo Stringa
- Department General Surgery, Liver, Pancreas and Intestinal Transplantation, Hospital Universitario, Fundacion Favaloro, Buenos Aires, Argentina
- Natalia Lausada
- Department General Surgery, Liver, Pancreas and Intestinal Transplantation, Hospital Universitario, Fundacion Favaloro, Buenos Aires, Argentina
- Maria Virginia Gentilini
- Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMETTyB, CONICET, Universidad Favaloro), Laboratorio de Inmunología asociada al Trasplante, Buenos Aires, Argentina
- Gabriel E. Gondolesi
- Department General Surgery, Liver, Pancreas and Intestinal Transplantation, Hospital Universitario, Fundacion Favaloro, Buenos Aires, Argentina
- Kai Bachmann
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Philipp Busch
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Rainer Grotelüschen
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Ioannis C. Maroulis
- Department of Surgery, University of Patras Medical School, Patras, Greece
- Petra C. Arck
- Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Ryosuke Nakano
- Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Angus W. Thomson
- Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Tarik Ghadban
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Michael Tachezy
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Nathaniel Melling
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Eike-Gert Achilles
- Department of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Victor G. Puelles
- III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Felix Nickel
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Oliver Mann
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Jakob R. Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Jun Li
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Nicola Gagliani
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Samuel Huber
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Anastasios D. Giannou
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- DOI
- https://doi.org/10.1080/2162402X.2023.2269634
- Journal volume & issue
-
Vol. 12,
no. 1
Abstract
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.
Keywords
