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@ARTICLE{Braun:298893,
author = {L. M. Braun and S. Giesler and G. Andrieux and R. Riemer
and N. Talvard-Balland and S. Duquesne and T. Rückert and
S. Unger and S. Kreutmair and M. Zwick and M. Follo and A.
Hartmann and N. Osswald and W. Melchinger and S. Chapman and
J. A. Hutchinson and S. Haferkamp and L. Torster and J.
Kött and C. Gebhardt and D. Hellwig and N. Karantzelis and
T. Wallrabenstein and T. Lowinus and M. Yücel and N. Brehm
and J. Rawluk and D. Pfeifer and P. Bronsert and M. Rogg and
S. Mattern and M. Heikenwälder$^*$ and S. Fusco and N. P.
Malek and S. Singer and A. Schmitt-Graeff and F. Ceteci and
F. R. Greten and B. R. Blazar and M. Börries$^*$ and N.
Köhler and J. Duyster$^*$ and G. Ihorst and S. Lassmann and
P. Keye and S. Minguet and D. Schadendorf$^*$ and S.
Ugurel$^*$ and D. Rafei-Shamsabadi and R. Thimme and P.
Hasselblatt and B. Bengsch$^*$ and C. Schell and E. L.
Pearce and F. Meiss and B. Becher and C. Funke-Lorenz$^*$
and J.-M. Placke$^*$ and P. Apostolova$^*$ and R.
Zeiser$^*$},
title = {{A}diponectin reduces immune checkpoint inhibitor-induced
inflammation without blocking anti-tumor immunity},
journal = {Cancer cell},
volume = {43},
number = {2},
issn = {1535-6108},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DKFZ-2025-00336},
pages = {269 - 291.e19},
year = {2025},
abstract = {Immune-related adverse events (irAEs) in cancer patients
receiving immune checkpoint inhibitors (ICIs) cause
morbidity and necessitate cessation of treatment. Comparing
irAE treatments, we find that anti-tumor immunity is
preserved in mice after extracorporeal photopheresis (ECP)
but reduced with glucocorticosteroids, TNFα blockade, and
α4β7-integrin inhibition. Local adiponectin production
elicits a tissue-specific effect by reducing
pro-inflammatory T cell frequencies in the colon while
sparing tumor-specific T cell development. A prospective
phase-1b/2 trial (EudraCT-No.2021-002073-26) with 14
patients reveals low ECP-related toxicity. Overall response
rate for all irAEs is $92\%$ $(95\%$ confidence interval
[CI]: $63.97\%–99.81\%);$ colitis-specific complete
remission rate is $100\%$ $(95\%$ CI: $63.06\%–100\%).$
Glucocorticosteroid dosages could be reduced for all
patients after ECP therapy. The ECP-adiponectin axis reduces
intestinal tissue-resident memory T cell activation and
CD4+IFN-γ+ T cells in patients with ICI-induced colitis
without evidence of loss of anti-tumor immunity. In
conclusion, we identify adiponectin as an immunomodulatory
molecule that controls ICI-induced irAEs without blocking
anti-tumor immunity.},
cin = {D440 / FR01 / ED01},
ddc = {610},
cid = {I:(DE-He78)D440-20160331 / I:(DE-He78)FR01-20160331 /
I:(DE-He78)ED01-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39933899},
doi = {10.1016/j.ccell.2025.01.004},
url = {https://inrepo02.dkfz.de/record/298893},
}