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. 2023 Oct 20;12(1):2269634.
doi: 10.1080/2162402X.2023.2269634. eCollection 2023.

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis

Tao Zhang  1   2 , Ramez Wahib  3 , Dimitra E Zazara  4   5 , Jöran Lücke  1   2   3 , Ahmad Mustafa Shiri  1 , Jan Kempski  1   2   6 , Lilan Zhao  3 , Theodora Agalioti  3 , Andres Pablo Machicote  1   2 , Olympia Giannou  7 , Ioannis Belios  4 , Rongrong Jia  1   2 , Siwen Zhang  1   2 , Joseph Tintelnot  6   8 , Hannes Seese  3 , Julia Kristin Grass  3 , Baris Mercanoglu  3 , Louisa Stern  3 , Pasquale Scognamiglio  3 , Mohammad Fard-Aghaie  3 , Philipp Seeger  3 , Jonas Wakker  3 , Marius Kemper  3 , Benjamin Brunswig  3 , Anna Duprée  3 , Panagis M Lykoudis  9   10 , Anastasia Pikouli  9 , Emmanouil Giorgakis  11   12 , Pablo Stringa  13 , Natalia Lausada  13 , Maria Virginia Gentilini  14 , Gabriel E Gondolesi  13 , Kai Bachmann  3 , Philipp Busch  3 , Rainer Grotelüschen  3 , Ioannis C Maroulis  15 , Petra C Arck  4 , Ryosuke Nakano  16 , Angus W Thomson  16   17 , Tarik Ghadban  3 , Michael Tachezy  3 , Nathaniel Melling  3 , Eike-Gert Achilles  18 , Victor G Puelles  19   20 , Felix Nickel  3 , Thilo Hackert  3 , Oliver Mann  3 , Jakob R Izbicki  3 , Jun Li  3 , Nicola Gagliani  1   2   3 , Samuel Huber  1   2 , Anastasios D Giannou  1   2   3
Affiliations

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis

Tao Zhang et al. Oncoimmunology. .

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: IL-22; Th22; liver metastasis.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Increased IL-22 levels in human liver metastasis.
Figure 2.
Figure 2.
Th22 cells are the main source of IL-22 in murine-established liver metastasis.
Figure 3.
Figure 3.
Th22 cells are the main source of IL-22 in established murine lung metastasis.
Figure 4.
Figure 4.
Lin- cells are not the main source of IL-22 in established murine liver metastasis.
Figure 5.
Figure 5.
Lin- cells are not the main source of IL-22 in established murine lung metastasis.
Figure 6.
Figure 6.
T cell- but not Th17-derived IL-22 plays a key role in liver and lung metastasis formation.
Figure 7.
Figure 7.
IL-22 promotes angiogenesis in established liver metastasis.
See this image and copyright information in PMC

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