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@ARTICLE{Nuez:212455,
author = {N. G. Nuñez and F. Berner and E. Friebel and S. Unger and
N. Wyss and J. M. Gomez and M.-T. Purde and R. Niederer and
M. Porsch and C. Lichtensteiger and R. Kramer and M. Erdmann
and C. Schmitt and L. Heinzerling and M.-T. Abdou and J.
Karbach and D. Schadendorf$^*$ and L. Zimmer and S. Ugurel
and N. Klümper and M. Hölzel and L. Power and S. Kreutmair
and M. Capone and G. Madonna and L. Cevhertas and A. Heider
and T. Amaral and O. Hasan Ali and D. Bomze and F. Dimitriou
and S. Diem and P. A. Ascierto and R. Dummer and E. Jäger
and C. Driessen and M. P. Levesque and W. van de Veen and M.
Joerger and M. Früh and B. Becher and L. Flatz},
title = {{I}mmune signatures predict development of autoimmune
toxicity in patients with cancer treated with immune
checkpoint inhibitors.},
journal = {Med},
volume = {4},
number = {2},
issn = {2666-6340},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {DKFZ-2023-00172},
pages = {113-129.e7},
year = {2023},
note = {2023 Feb 10;4(2):113-129.e7},
abstract = {Immune checkpoint inhibitors (ICIs) are among the most
promising treatment options for melanoma and non-small cell
lung cancer (NSCLC). While ICIs can induce effective
anti-tumor responses, they may also drive serious
immune-related adverse events (irAEs). Identifying
biomarkers to predict which patients will suffer from irAEs
would enable more accurate clinical risk-benefit analysis
for ICI treatment and may also shed light on common or
distinct mechanisms underpinning treatment success and
irAEs.In this prospective multi-center study, we combined a
multi-omics approach including unbiased single-cell
profiling of over 300 peripheral blood mononuclear cell
(PBMC) samples and high-throughput proteomics analysis of
over 500 serum samples to characterize the systemic immune
compartment of patients with melanoma or NSCLC before and
during treatment with ICIs.When we combined the parameters
obtained from the multi-omics profiling of patient blood and
serum, we identified potential predictive biomarkers for
ICI-induced irAEs. Specifically, an early increase in
CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks
after the start of therapy are likely indicators of
heightened risk of developing irAEs. In addition, an early
expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+
CD8+ T cells is also likely to be associated with increased
risk of irAEs.We suggest that the combination of these
cellular and proteomic biomarkers may help to predict which
patients are likely to benefit most from ICI therapy and
those requiring intensive monitoring for irAEs.This work was
primarily funded by the European Research Council, the Swiss
National Science Foundation, the Swiss Cancer League, and
the Forschungsförderung of the Kantonsspital St. Gallen.},
keywords = {Translation to patients (Other) / biomarkers for
immunotherapy (Other) / cancer immunotherapy (Other) /
checkpoint blockade (Other) / immune-related adverse events
(Other)},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36693381},
doi = {10.1016/j.medj.2022.12.007},
url = {https://inrepo02.dkfz.de/record/212455},
}