%0 Journal Article
%A Haake, Markus
%A Haack, Beatrice
%A Schäfer, Tina
%A Harter, Patrick
%A Mattavelli, Greta
%A Eiring, Patrick
%A Vashist, Neha
%A Wedekink, Florian
%A Genssler, Sabrina
%A Fischer, Birgitt
%A Dahlhoff, Julia
%A Mokhtari, Fatemeh
%A Kuzkina, Anastasia
%A Welters, Marij J P
%A Benz, Tamara M
%A Sorger, Lena
%A Thiemann, Vincent
%A Almanzar, Giovanni
%A Selle, Martina
%A Thein, Klara
%A Späth, Jacob
%A Gonzalez, Maria Cecilia
%A Reitinger, Carmen
%A Ipsen-Escobedo, Andrea
%A Wistuba-Hamprecht, Kilian
%A Eichler, Kristin
%A Filipski, Katharina
%A Zeiner, Pia S
%A Beschorner, Rudi
%A Goedemans, Renske
%A Gogolla, Falk Hagen
%A Hackl, Hubert
%A Rooswinkel, Rogier W
%A Thiem, Alexander
%A Roche, Paula Romer
%A Joshi, Hemant
%A Pühringer, Dirk
%A Wöckel, Achim
%A Diessner, Joachim E
%A Rüdiger, Manfred
%A Leo, Eugen
%A Cheng, Phil F
%A Levesque, Mitchell P
%A Goebeler, Matthias
%A Sauer, Markus
%A Nimmerjahn, Falk
%A Schuberth-Wagner, Christine
%A von Felten, Stefanie
%A Mittelbronn, Michel
%A Mehling, Matthias
%A Beilhack, Andreas
%A van der Burg, Sjoerd H
%A Riedel, Angela
%A Weide, Benjamin
%A Dummer, Reinhard
%A Wischhusen, Jörg
%T Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment.
%J Nature Communications
%V 14
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DKFZ-2023-01428
%P 4253
%D 2023
%X 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.
%K Humans
%K Mice
%K Animals
%K T-Lymphocytes: pathology
%K Lymphocyte Function-Associated Antigen-1
%K Endothelial Cells: pathology
%K Immune Checkpoint Inhibitors: pharmacology
%K Immune Checkpoint Inhibitors: therapeutic use
%K Melanoma: pathology
%K Immunotherapy
%K Tumor Microenvironment
%K Lymphocyte Function-Associated Antigen-1 (NLM Chemicals)
%K Immune Checkpoint Inhibitors (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37474523
%2 pmc:PMC10359308
%R 10.1038/s41467-023-39817-3
%U https://inrepo02.dkfz.de/record/277711