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@ARTICLE{Haake:277711,
author = {M. Haake and B. Haack and T. Schäfer and P. Harter$^*$ and
G. Mattavelli and P. Eiring and N. Vashist and F. Wedekink
and S. Genssler and B. Fischer and J. Dahlhoff and F.
Mokhtari and A. Kuzkina and M. J. P. Welters and T. M. Benz
and L. Sorger and V. Thiemann and G. Almanzar and M. Selle
and K. Thein and J. Späth and M. C. Gonzalez and C.
Reitinger and A. Ipsen-Escobedo and K. Wistuba-Hamprecht and
K. Eichler and K. Filipski$^*$ and P. S. Zeiner$^*$ and R.
Beschorner and R. Goedemans and F. H. Gogolla and H. Hackl
and R. W. Rooswinkel and A. Thiem and P. R. Roche and H.
Joshi and D. Pühringer and A. Wöckel and J. E. Diessner
and M. Rüdiger and E. Leo and P. F. Cheng and M. P.
Levesque and M. Goebeler and M. Sauer and F. Nimmerjahn and
C. Schuberth-Wagner and S. von Felten and M. Mittelbronn and
M. Mehling and A. Beilhack and S. H. van der Burg and A.
Riedel and B. Weide and R. Dummer and J. Wischhusen},
title = {{T}umor-derived {GDF}-15 blocks {LFA}-1 dependent {T} cell
recruitment and suppresses responses to anti-{PD}-1
treatment.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-01428},
pages = {4253},
year = {2023},
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.},
keywords = {Humans / Mice / Animals / T-Lymphocytes: pathology /
Lymphocyte Function-Associated Antigen-1 / Endothelial
Cells: pathology / Immune Checkpoint Inhibitors:
pharmacology / Immune Checkpoint Inhibitors: therapeutic use
/ Melanoma: pathology / Immunotherapy / Tumor
Microenvironment / Lymphocyte Function-Associated Antigen-1
(NLM Chemicals) / Immune Checkpoint Inhibitors (NLM
Chemicals)},
cin = {FM01},
ddc = {500},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37474523},
pmc = {pmc:PMC10359308},
doi = {10.1038/s41467-023-39817-3},
url = {https://inrepo02.dkfz.de/record/277711},
}