IL-22BP controls the progression of liver metastasis in colorectal cancer

Anastasios D Giannou; Jan Kempski; Tao Zhang; Jöran Lücke; Ahmad Mustafa Shiri; Dimitra E Zazara; Ioannis Belios; Andres Machicote; Philipp Seeger; Theodora Agalioti; Joseph Tintelnot; Adrian Sagebiel; Miriam Tomczak; Lennart Bauditz; Tanja Bedke; Lorenz Kocheise; Baris Mercanoglu; Mohammad Fard-Aghaie; Emmanouil Giorgakis; Panagis M Lykoudis; Anastasia Pikouli; Julia-Kristin Grass; Ramez Wahib; Jan Bardenhagen; Benjamin Brunswig; Asmus Heumann; Tarik Ghadban; Anna Duprée; Michael Tachezy; Nathaniel Melling; Petra C Arck; Pablo Stringa; Maria Virginia Gentilini; Gabriel E Gondolesi; Ryosuke Nakano; Angus W Thomson; Daniel Perez; Jun Li; Oliver Mann; Jakob R Izbicki; Nicola Gagliani; Ioannis C Maroulis; Samuel Huber

doi:10.3389/fonc.2023.1170502

IL-22BP controls the progression of liver metastasis in colorectal cancer

Front Oncol. 2023 May 31:13:1170502. doi: 10.3389/fonc.2023.1170502. eCollection 2023.

Authors

Anastasios D Giannou^{1

2

3

4}, Jan Kempski^{1

2

5}, Tao Zhang^{1

2}, Jöran Lücke^{1

2

3}, Ahmad Mustafa Shiri^{1

2}, Dimitra E Zazara^{6

7}, Ioannis Belios⁷, Andres Machicote^{1

2}, Philipp Seeger³, Theodora Agalioti³, Joseph Tintelnot^{5

8}, Adrian Sagebiel³, Miriam Tomczak^{1

2}, Lennart Bauditz^{1

2}, Tanja Bedke^{1

2}, Lorenz Kocheise^{1

2}, Baris Mercanoglu³, Mohammad Fard-Aghaie³, Emmanouil Giorgakis^{9

10}, Panagis M Lykoudis^{11

12}, Anastasia Pikouli¹¹, Julia-Kristin Grass³, Ramez Wahib³, Jan Bardenhagen³, Benjamin Brunswig³, Asmus Heumann³, Tarik Ghadban³, Anna Duprée³, Michael Tachezy³, Nathaniel Melling³, Petra C Arck⁷, Pablo Stringa¹³, Maria Virginia Gentilini¹⁴, Gabriel E Gondolesi¹³, Ryosuke Nakano¹⁵, Angus W Thomson^{15

16}, Daniel Perez³, Jun Li³, Oliver Mann³, Jakob R Izbicki³, Nicola Gagliani^{2

3}, Ioannis C Maroulis⁴, Samuel Huber^{1

2}

Affiliations

¹ Section of Molecular Immunology und Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
² Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³ Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴ Department of Surgery, University of Patras Medical School, Patras, Greece.
⁵ Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶ Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Laboratory for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁸ ll. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁹ Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
¹⁰ Division of Transplantation, Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
¹¹ 3rd Department of Surgery, Attiko University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
¹² Division of Surgery and Interventional Science, University College London (UCL), London, United Kingdom.
¹³ Department General Surgery, Liver, Pancreas and Intestinal Transplantation, Hospital Universitario, Fundacion Favaloro, Buenos Aires, Argentina.
¹⁴ Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMETTyB, Concejo Nacional de Investigaciones Científicas y tecnológicas (CONICET), Universidad Favaloro), Laboratorio de Inmunología Asociada al Trasplante, Buenos Aires, Argentina.
¹⁵ Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
¹⁶ Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

Abstract

Background: The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown.

Methods: We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages.

Results: Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice.

Conclusions: We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC.

Keywords: IL-22BP; cancer therapy; colorectal cancer; metastasis; tumor immunology.

Copyright © 2023 Giannou, Kempski, Zhang, Lücke, Shiri, Zazara, Belios, Machicote, Seeger, Agalioti, Tintelnot, Sagebiel, Tomczak, Bauditz, Bedke, Kocheise, Mercanoglu, Fard-Aghaie, Giorgakis, Lykoudis, Pikouli, Grass, Wahib, Bardenhagen, Brunswig, Heumann, Ghadban, Duprée, Tachezy, Melling, Arck, Stringa, Gentilini, Gondolesi, Nakano, Thomson, Perez, Li, Mann, Izbicki, Gagliani, Maroulis and Huber.

Grants and funding

This work was supported in part by the Deutsche Forschungsgemeinschaft (grant SFB841 to SH, NG, and grant SFB1328 to SH, NG), the European Research Council (CoG865466 to SH), Ernst Jung-Stiftung Hamburg (to SH), Stiftung Experimentelle Biomedizin (to SH), European Respiratory Society/short term fellowship (to AG), Else Kröner Memorial Stipendium (to AG), Werner Otto Stiftung (to AG), Erich und Gertrud Roggenbuck Stiftung (to AG), Hamburger Krebsgesellschaft Stiftung (to AG), Mildred Scheel Cancer Career Center Hamburg HaTriCS4 short term fellowship funded by Deutsche Krebshilfe (to JK, JT) and China Scholarship Council (to TZ). SH has an endowed Heisenberg - Professorship awarded by the Deutsche Forschungsgemeinschaft.