Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment

Markus Haake, Beatrice Haack, Tina Schäfer, Patrick N. Harter, Greta Mattavelli, Patrick Eiring, Neha Vashist, Florian Wedekink, Sabrina Genssler, Birgitt Fischer, Julia Dahlhoff, Fatemeh Mokhtari, Anastasia Kuzkina, Marij J. P. Welters, Tamara M. Benz, Lena Sorger, Vincent Thiemann, Giovanni Almanzar, Martina Selle, Klara Thein, Jacob Späth, Maria Cecilia Gonzalez, Carmen Reitinger, Andrea Ipsen-Escobedo, Kilian Wistuba-Hamprecht, Kristin Eichler, Katharina Filipski, Pia S. Zeiner, Rudi Beschorner, Renske Goedemans, Falk Hagen Gogolla, Hubert Hackl, Rogier W. Rooswinkel, Alexander Thiem, Paula Romer Roche, Hemant Joshi, Dirk Pühringer, Achim Wöckel, Joachim E. Diessner, Manfred Rüdiger, Eugen Leo, Phil F. Cheng, Mitchell P. Levesque, Matthias Goebeler, Markus Sauer, Falk Nimmerjahn, Christine Schuberth-Wagner, Stefanie Felten, Michel Mittelbronn, Matthias Mehling, Andreas Beilhack, Sjoerd H. Burg, Angela Riedel, Benjamin Weide, Reinhard Dummer and Jörg Wischhusen ()
Additional contact information
Markus Haake: University Hospital Würzburg
Beatrice Haack: University Hospital Würzburg
Tina Schäfer: University Hospital Würzburg
Patrick N. Harter: German Cancer Research Center (DKFZ)
Greta Mattavelli: University Hospital of Würzburg
Patrick Eiring: Julius Maximilians University Würzburg, Am Hubland
Neha Vashist: University Hospital Würzburg
Florian Wedekink: University Hospital Würzburg
Sabrina Genssler: CatalYm GmbH
Birgitt Fischer: University Hospital Würzburg
Julia Dahlhoff: University Hospital of Würzburg
Fatemeh Mokhtari: University Hospital of Würzburg
Anastasia Kuzkina: University Hospital Würzburg
Marij J. P. Welters: Leiden University Medical Center
Tamara M. Benz: University Hospital Würzburg
Lena Sorger: University Hospital Würzburg
Vincent Thiemann: University Hospital Würzburg
Giovanni Almanzar: University Hospital Würzburg
Martina Selle: University Hospital Würzburg
Klara Thein: University Hospital Würzburg
Jacob Späth: University Hospital Würzburg
Maria Cecilia Gonzalez: CatalYm GmbH
Carmen Reitinger: University of Erlangen
Andrea Ipsen-Escobedo: University of Erlangen
Kilian Wistuba-Hamprecht: University Medical Center Tübingen
Kristin Eichler: University Hospital Würzburg
Katharina Filipski: German Cancer Research Center (DKFZ)
Pia S. Zeiner: German Cancer Research Center (DKFZ)
Rudi Beschorner: University of Tübingen
Renske Goedemans: Leiden University Medical Center
Falk Hagen Gogolla: Medical University of Innsbruck
Hubert Hackl: Medical University of Innsbruck
Rogier W. Rooswinkel: Forbion
Alexander Thiem: University Hospital Würzburg
Paula Romer Roche: University Hospital Würzburg
Hemant Joshi: University Hospital Würzburg
Dirk Pühringer: University Hospital Würzburg
Achim Wöckel: University Hospital Würzburg
Joachim E. Diessner: University Hospital Würzburg
Manfred Rüdiger: CatalYm GmbH
Eugen Leo: CatalYm GmbH
Phil F. Cheng: University of Zurich Hospital
Mitchell P. Levesque: University of Zurich Hospital
Matthias Goebeler: University Hospital Würzburg
Markus Sauer: Julius Maximilians University Würzburg, Am Hubland
Falk Nimmerjahn: University of Erlangen
Christine Schuberth-Wagner: CatalYm GmbH
Stefanie Felten: oikostat GmbH, Statistical Analyses and Consulting
Michel Mittelbronn: Luxembourg Institute of Health (LIH)
Matthias Mehling: University Hospital Basel
Andreas Beilhack: University Hospital of Würzburg
Sjoerd H. Burg: Leiden University Medical Center
Angela Riedel: University Hospital of Würzburg
Benjamin Weide: University Medical Center Tübingen
Reinhard Dummer: Forbion
Jörg Wischhusen: University Hospital Würzburg

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39817-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39817-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39817-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().