Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22

Anastasios D. Giannou; Jan Kempski; Ahmad Mustafa Shiri; Jöran Lücke; Tao Zhang; Lilan Zhao; Dimitra E. Zazara; Filippo Cortesi; Kristoffer Riecken; Maria Carolina Amezcua Vesely; Jun Siong Low; Hao Xu; Eleanna Kaffe; Laura Garcia-Perez; Theodora Agalioti; Yoshito Yamada; Wolfgang Jungraithmayr; Ehud Zigmond; Karl Frederick Karstens; Babett Steglich; Jonas Wagner; Leonie Konczalla; Antonella Carambia; Kornelius Schulze; Johann von Felden; Peter May; Daria Briukhovetska; Tanja Bedke; Leonie Brockmann; Sarah Starzonek; Tobias Lange; Claudia Koch; Sabine Riethdorf; Penelope Pelczar; Marius Böttcher; Morsal Sabihi; Francis J. Huber; Matthias Reeh; Julia Kristin Grass; Ramez Wahib; Hannes Seese; Björn Ole Stüben; Mohammad Fard-Aghaie; Anna Duprée; Pasquale Scognamiglio; Gabriel Plitzko; Jan Meiners; Shiwa Soukou; Agnes Wittek; Caroline Manthey; Ioannis C. Maroulis; Petra C. Arck; Daniel Perez; Bin Gao; Sotirios G. Zarogiannis; Till Strowig; Renata Pasqualini; Wadih Arap; Javier Suárez Gosálvez; Sebastian Kobold; Immo Prinz; Andreas H. Guse; Michael Tachezy; Tarik Ghadban; Asmus Heumann; Jun Li; Nathaniel Melling; Oliver Mann; Jakob R. Izbicki; Klaus Pantel; Udo Schumacher; Ansgar W. Lohse; Richard A. Flavell; Nicola Gagliani; Samuel Huber

doi:10.1016/j.immuni.2022.12.014

Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22

Anastasios D. Giannou^*, Jan Kempski, Ahmad Mustafa Shiri, Jöran Lücke, Tao Zhang, Lilan Zhao, Dimitra E. Zazara, Filippo Cortesi, Kristoffer Riecken, Maria Carolina Amezcua Vesely, Jun Siong Low, Hao Xu, Eleanna Kaffe, Laura Garcia-Perez, Theodora Agalioti, Yoshito Yamada, Wolfgang Jungraithmayr, Ehud Zigmond, Karl Frederick Karstens, Babett SteglichJonas Wagner, Leonie Konczalla, Antonella Carambia, Kornelius Schulze, Johann von Felden, Peter May, Daria Briukhovetska, Tanja Bedke, Leonie Brockmann, Sarah Starzonek, Tobias Lange, Claudia Koch, Sabine Riethdorf, Penelope Pelczar, Marius Böttcher, Morsal Sabihi, Francis J. Huber, Matthias Reeh, Julia Kristin Grass, Ramez Wahib, Hannes Seese, Björn Ole Stüben, Mohammad Fard-Aghaie, Anna Duprée, Pasquale Scognamiglio, Gabriel Plitzko, Jan Meiners, Shiwa Soukou, Agnes Wittek, Caroline Manthey, Ioannis C. Maroulis, Petra C. Arck, Daniel Perez, Bin Gao, Sotirios G. Zarogiannis, Till Strowig, Renata Pasqualini, Wadih Arap, Javier Suárez Gosálvez, Sebastian Kobold, Immo Prinz, Andreas H. Guse, Michael Tachezy, Tarik Ghadban, Asmus Heumann, Jun Li, Nathaniel Melling, Oliver Mann, Jakob R. Izbicki, Klaus Pantel, Udo Schumacher, Ansgar W. Lohse, Richard A. Flavell, Nicola Gagliani, Samuel Huber^*

^*Corresponding author for this work

Internal Medicine

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

Original language	English
Pages (from-to)	125-142.e12
Journal	Immunity
Volume	56
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2022.12.014
State	Published - 10 Jan 2023

Funding

Funders	Funder number
Tabby Therapeutics
Novartis Pharmaceuticals Corporation
Jung-Stiftung für Wissenschaft und Forschung
Hamburger Krebsgesellschaft Stiftung
National Institutes of Health
European Commission
Associazione Italiana per la Ricerca sul Cancro
Erich und Gertrud Roggenbuck-Stiftung
F. Hoffmann-La Roche
Novartis
TCR2, Inc.
Deutsches Zentrum für Infektionsforschung
Alexander von Humboldt-Stiftung
Arcus Biosciences
Howard Hughes Medical Institute
Horizon 2020	765492
European Research Council	StG 756017
Horizon 2020 Framework Programme	715271, 800924, 865466
Deutsche Forschungsgemeinschaft	SFB-TRR 338/1 2021–452881907, SFB1328, LA3373/6-1, 50552-1, SFB841
Deutsche Krebshilfe	70112504, 834974

Keywords

ANPEP
IL-22
cancer cell extravasation
endothelial cells
extravasation
metastasis
metastasis formation
tissue resident cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.immuni.2022.12.014

Cite this

Giannou, A. D., Kempski, J., Shiri, A. M., Lücke, J., Zhang, T., Zhao, L., Zazara, D. E., Cortesi, F., Riecken, K., Amezcua Vesely, M. C., Low, J. S., Xu, H., Kaffe, E., Garcia-Perez, L., Agalioti, T., Yamada, Y., Jungraithmayr, W., Zigmond, E., Karstens, K. F., ... Huber, S. (2023). Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22. Immunity, 56(1), 125-142.e12. https://doi.org/10.1016/j.immuni.2022.12.014

@article{6c192b19d63d4c8eb42a96158962f639,

title = "Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22",

abstract = "During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.",

keywords = "ANPEP, IL-22, cancer cell extravasation, endothelial cells, extravasation, metastasis, metastasis formation, tissue resident cells",

author = "Giannou, {Anastasios D.} and Jan Kempski and Shiri, {Ahmad Mustafa} and J{\"o}ran L{\"u}cke and Tao Zhang and Lilan Zhao and Zazara, {Dimitra E.} and Filippo Cortesi and Kristoffer Riecken and {Amezcua Vesely}, {Maria Carolina} and Low, {Jun Siong} and Hao Xu and Eleanna Kaffe and Laura Garcia-Perez and Theodora Agalioti and Yoshito Yamada and Wolfgang Jungraithmayr and Ehud Zigmond and Karstens, {Karl Frederick} and Babett Steglich and Jonas Wagner and Leonie Konczalla and Antonella Carambia and Kornelius Schulze and {von Felden}, Johann and Peter May and Daria Briukhovetska and Tanja Bedke and Leonie Brockmann and Sarah Starzonek and Tobias Lange and Claudia Koch and Sabine Riethdorf and Penelope Pelczar and Marius B{\"o}ttcher and Morsal Sabihi and Huber, {Francis J.} and Matthias Reeh and Grass, {Julia Kristin} and Ramez Wahib and Hannes Seese and St{\"u}ben, {Bj{\"o}rn Ole} and Mohammad Fard-Aghaie and Anna Dupr{\'e}e and Pasquale Scognamiglio and Gabriel Plitzko and Jan Meiners and Shiwa Soukou and Agnes Wittek and Caroline Manthey and Maroulis, {Ioannis C.} and Arck, {Petra C.} and Daniel Perez and Bin Gao and Zarogiannis, {Sotirios G.} and Till Strowig and Renata Pasqualini and Wadih Arap and Gos{\'a}lvez, {Javier Su{\'a}rez} and Sebastian Kobold and Immo Prinz and Guse, {Andreas H.} and Michael Tachezy and Tarik Ghadban and Asmus Heumann and Jun Li and Nathaniel Melling and Oliver Mann and Izbicki, {Jakob R.} and Klaus Pantel and Udo Schumacher and Lohse, {Ansgar W.} and Flavell, {Richard A.} and Nicola Gagliani and Samuel Huber",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2023",

month = jan,

day = "10",

doi = "10.1016/j.immuni.2022.12.014",

language = "אנגלית",

volume = "56",

pages = "125--142.e12",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "1",

}

Giannou, AD, Kempski, J, Shiri, AM, Lücke, J, Zhang, T, Zhao, L, Zazara, DE, Cortesi, F, Riecken, K, Amezcua Vesely, MC, Low, JS, Xu, H, Kaffe, E, Garcia-Perez, L, Agalioti, T, Yamada, Y, Jungraithmayr, W, Zigmond, E, Karstens, KF, Steglich, B, Wagner, J, Konczalla, L, Carambia, A, Schulze, K, von Felden, J, May, P, Briukhovetska, D, Bedke, T, Brockmann, L, Starzonek, S, Lange, T, Koch, C, Riethdorf, S, Pelczar, P, Böttcher, M, Sabihi, M, Huber, FJ, Reeh, M, Grass, JK, Wahib, R, Seese, H, Stüben, BO, Fard-Aghaie, M, Duprée, A, Scognamiglio, P, Plitzko, G, Meiners, J, Soukou, S, Wittek, A, Manthey, C, Maroulis, IC, Arck, PC, Perez, D, Gao, B, Zarogiannis, SG, Strowig, T, Pasqualini, R, Arap, W, Gosálvez, JS, Kobold, S, Prinz, I, Guse, AH, Tachezy, M, Ghadban, T, Heumann, A, Li, J, Melling, N, Mann, O, Izbicki, JR, Pantel, K, Schumacher, U, Lohse, AW, Flavell, RA, Gagliani, N & Huber, S 2023, 'Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22', Immunity, vol. 56, no. 1, pp. 125-142.e12. https://doi.org/10.1016/j.immuni.2022.12.014

TY - JOUR

T1 - Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22

AU - Giannou, Anastasios D.

AU - Kempski, Jan

AU - Shiri, Ahmad Mustafa

AU - Lücke, Jöran

AU - Zhang, Tao

AU - Zhao, Lilan

AU - Zazara, Dimitra E.

AU - Cortesi, Filippo

AU - Riecken, Kristoffer

AU - Amezcua Vesely, Maria Carolina

AU - Low, Jun Siong

AU - Xu, Hao

AU - Kaffe, Eleanna

AU - Garcia-Perez, Laura

AU - Agalioti, Theodora

AU - Yamada, Yoshito

AU - Jungraithmayr, Wolfgang

AU - Zigmond, Ehud

AU - Karstens, Karl Frederick

AU - Steglich, Babett

AU - Wagner, Jonas

AU - Konczalla, Leonie

AU - Carambia, Antonella

AU - Schulze, Kornelius

AU - von Felden, Johann

AU - May, Peter

AU - Briukhovetska, Daria

AU - Bedke, Tanja

AU - Brockmann, Leonie

AU - Starzonek, Sarah

AU - Lange, Tobias

AU - Koch, Claudia

AU - Riethdorf, Sabine

AU - Pelczar, Penelope

AU - Böttcher, Marius

AU - Sabihi, Morsal

AU - Huber, Francis J.

AU - Reeh, Matthias

AU - Grass, Julia Kristin

AU - Wahib, Ramez

AU - Seese, Hannes

AU - Stüben, Björn Ole

AU - Fard-Aghaie, Mohammad

AU - Duprée, Anna

AU - Scognamiglio, Pasquale

AU - Plitzko, Gabriel

AU - Meiners, Jan

AU - Soukou, Shiwa

AU - Wittek, Agnes

AU - Manthey, Caroline

AU - Maroulis, Ioannis C.

AU - Arck, Petra C.

AU - Perez, Daniel

AU - Gao, Bin

AU - Zarogiannis, Sotirios G.

AU - Strowig, Till

AU - Pasqualini, Renata

AU - Arap, Wadih

AU - Gosálvez, Javier Suárez

AU - Kobold, Sebastian

AU - Prinz, Immo

AU - Guse, Andreas H.

AU - Tachezy, Michael

AU - Ghadban, Tarik

AU - Heumann, Asmus

AU - Li, Jun

AU - Melling, Nathaniel

AU - Mann, Oliver

AU - Izbicki, Jakob R.

AU - Pantel, Klaus

AU - Schumacher, Udo

AU - Lohse, Ansgar W.

AU - Flavell, Richard A.

AU - Gagliani, Nicola

AU - Huber, Samuel

PY - 2023/1/10

Y1 - 2023/1/10

N2 - During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

AB - During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

KW - ANPEP

KW - IL-22

KW - cancer cell extravasation

KW - endothelial cells

KW - extravasation

KW - metastasis

KW - metastasis formation

KW - tissue resident cells

UR - http://www.scopus.com/inward/record.url?scp=85146043104&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2022.12.014

DO - 10.1016/j.immuni.2022.12.014

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 36630911

AN - SCOPUS:85146043104

SN - 1074-7613

VL - 56

SP - 125-142.e12

JO - Immunity

JF - Immunity

IS - 1

ER -

Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22

Abstract

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this