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Haake, Markus; Haack, Beatrice; Schäfer, Tina; Harter, Patrick N.; Mattavelli, Greta; Eiring, Patrick; Vashist, Neha; Wedekink, Florian; Genssler, Sabrina; Fischer, Birgitt; Dahlhoff, Julia; Mokhtari, Fatemeh; Kuzkina, Anastasia; Welters, Marij J. P.; Benz, Tamara M.; Sorger, Lena; Thiemann, Vincent; Almanzar, Giovanni; Selle, Martina; Thein, Klara; Späth, Jacob; Gonzalez, Maria Cecilia; Reitinger, Carmen; Ipsen-Escobedo, Andrea; [...]

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

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  • Medientyp: E-Artikel
  • Titel: Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment
  • Beteiligte: Haake, Markus; Haack, Beatrice; Schäfer, Tina; Harter, Patrick N.; Mattavelli, Greta; Eiring, Patrick; Vashist, Neha; Wedekink, Florian; Genssler, Sabrina; Fischer, Birgitt; Dahlhoff, Julia; Mokhtari, Fatemeh; Kuzkina, Anastasia; Welters, Marij J. P.; Benz, Tamara M.; Sorger, Lena; Thiemann, Vincent; Almanzar, Giovanni; Selle, Martina; Thein, Klara; Späth, Jacob; Gonzalez, Maria Cecilia; Reitinger, Carmen; Ipsen-Escobedo, Andrea; [...]
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-023-39817-3
  • ISSN: 2041-1723
  • Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Entstehung:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
  • Zugangsstatus: Freier Zugang