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@ARTICLE{Gebhardt:126575,
author = {C. Gebhardt$^*$ and A. Sevko$^*$ and H. Jiang$^*$ and R.
Lichtenberger$^*$ and M. Reith$^*$ and K. Tarnanidis$^*$ and
T. Holland-Letz$^*$ and L. Umansky$^*$ and P. Beckhove$^*$
and A. Sucker and D. Schadendorf and J. Utikal$^*$ and V.
Umansky$^*$},
title = {{M}yeloid {C}ells and {R}elated {C}hronic {I}nflammatory
{F}actors as {N}ovel {P}redictive {M}arkers in {M}elanoma
{T}reatment with {I}pilimumab.},
journal = {Clinical cancer research},
volume = {21},
number = {24},
issn = {1557-3265},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DKFZ-2017-02603},
pages = {5453 - 5459},
year = {2015},
abstract = {Immunotherapy with ipilimumab improves the survival of
patients with metastatic melanoma. Because only around
$20\%$ of patients experience long-term benefit, reliable
markers are needed to predict a clinical response.
Therefore, we sought to determine if some myeloid cells and
related inflammatory mediators could serve as predictive
factors for the patients' response to ipilimumab.We
performed an analysis of myeloid cells in the peripheral
blood of 59 stage IV melanoma patients before the treatment
and at different time points upon the therapy using a
clinical laboratory analysis and multicolor flow cytometry.
In addition, the production of related inflammatory factors
was evaluated by ELISA or Bio-Plex assays.An early increase
in eosinophil count during the treatment with ipilimumab was
associated with an improved clinical response. In contrast,
elevated amounts of monocytic myeloid-derived suppressor
cells (moMDSC), neutrophils, and monocytes were found in
nonresponders (n = 36) as compared with basal levels and
with responding patients (n = 23). Moreover, in
nonresponders, moMDSCs produced significantly more nitric
oxide, and granulocytic MDSCs expressed higher levels of
PD-L1 than these parameters at baseline and in responders,
suggesting their enhanced immunosuppressive capacity. Upon
the first ipilimumab infusion, nonresponders displayed
elevated serum concentrations of S100A8/A9 and HMGB1 that
attract and activate MDSCs.These findings highlight
additional mechanisms of ipilimumab effects and suggest
levels of eosinophils, MDSCs, as well as related
inflammatory factors S100A8/A9 and HMGB1 as novel complex
predictive markers for patients who may benefit from the
ipilimumab therapy. Clin Cancer Res; 21(24); 5453-9. ©2015
AACR.},
keywords = {Antibodies, Monoclonal (NLM Chemicals) / Antineoplastic
Agents (NLM Chemicals) / Biomarkers (NLM Chemicals) /
Inflammation Mediators (NLM Chemicals) / ipilimumab (NLM
Chemicals)},
cin = {C060 / G300 / D015 / L401},
ddc = {610},
cid = {I:(DE-He78)C060-20160331 / I:(DE-He78)G300-20160331 /
I:(DE-He78)D015-20160331 / I:(DE-He78)L401-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26289067},
doi = {10.1158/1078-0432.CCR-15-0676},
url = {https://inrepo02.dkfz.de/record/126575},
}