학술논문
CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis
Document Type
article
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
Source
OncoImmunology, Vol 12, Iss 1 (2023)
Subject
Language
English
ISSN
2162402X
2162-402X
2162-402X
Abstract
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.