Foxp3 + Treg-derived IL-10 promotes colorectal cancer-derived lung metastasis.

Autor:	Shiri AM; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Fard-Aghaie M; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Bedke T; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Papazoglou ED; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Sabihi M; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Zazara DE; Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Zhang S; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Lücke J; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Seeger P; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Evers M; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asklepios Hospital Barmbek, Hamburg, Germany.; Semmelweis University Budapest, Asklepios Campus Hamburg, Hamburg, Germany., Hackert T; University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Oldhafer KJ; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asklepios Hospital Barmbek, Hamburg, Germany.; Semmelweis University Budapest, Asklepios Campus Hamburg, Hamburg, Germany., Gondolesi GE; General Surgery, Liver, Pancreas and Intestinal Transplantat Unit, Hospital Universitario-Fundación Favaloro, Buenos Aires, Argentina., Huber S; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany., Giannou AD; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. a.giannou@uke.de.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. a.giannou@uke.de.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. a.giannou@uke.de.; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asklepios Hospital Barmbek, Hamburg, Germany. a.giannou@uke.de.; Semmelweis University Budapest, Asklepios Campus Hamburg, Hamburg, Germany. a.giannou@uke.de.; General Surgery, Liver, Pancreas and Intestinal Transplantat Unit, Hospital Universitario-Fundación Favaloro, Buenos Aires, Argentina. a.giannou@uke.de.; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, Center of Internal Medicine and Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. a.giannou@uke.de.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2024 Dec 16; Vol. 14 (1), pp. 30483. Date of Electronic Publication: 2024 Dec 16.
DOI:	10.1038/s41598-024-80437-8
Abstrakt:	The lung is one of the most frequently metastasized organs from various cancer entities, especially colorectal cancer (CRC). The occurrence of lung metastasis correlates with worse prognosis in CRC patients. Here, we aimed to investigate the role of IL-10 in lung metastasis development and identify the cellular source and target cells of IL-10 during lung metastatic establishment. To induce lung metastasis in mice, we injected MC38 murine colon cancer cells intravenously. Mice with Il10-deficiency were used to test the role of IL-10. The lung metastatic burden was assessed both macroscopically and histologically. IL-10- and Foxp3-reporter mice were employed to identify the cellular source and target cells of IL-10 in lung metastasis using flow cytometry. These findings were further confirmed using mice with cell-specific deletion of Il10- and IL-10 receptor (Il10ra). Interestingly, Il10 ablation led to reduced lung metastasis formation, suggesting a pathogenic role of IL-10 in lung metastasis. Moreover, using reporter mice, we identified Foxp3 + regulatory T cells (Tregs) as the predominant cellular source of IL-10 in lung metastasis. Accordingly, Foxp3 + Treg-specific deletion of Il10 resulted in decreased lung metastasis formation. In terms of target cells, myeloid cells and Foxp3 + Tregs expressed high IL-10Ra levels. Indeed, IL-10 signaling blockade in these two immune cell populations resulted in reduced lung metastatic burden. In conclusion, Foxp3 + Treg-derived IL-10 was found to act on Foxp3 + Tregs and myeloid cells, thereby promoting lung metastasis formation. These findings provide insights into lung metastasis-related immunity and establish the groundwork for optimizing metastasis-targeting immunotherapies through targeting of IL-10 as a novel therapeutic strategy. Competing Interests: Competing interests: The authors declare no competing interests. (© 2024. The Author(s).)
Databáze:	MEDLINE
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