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@ARTICLE{Struckmeier:181140,
author = {A.-K. Struckmeier and A. Radermacher and M. Fehrenz and T.
Bellin and D. Alansary and P. Wartenberg and U. Boehm and M.
Wagner and A. Scheller and J. Hess$^*$ and J. Moratin and C.
Freudlsperger and J. Hoffmann and L. Thurner and K. Roemer
and K. Freier and D. Horn},
title = {{IDO}1 is highly expressed in macrophages of patients in
advanced tumour stages of oral squamous cell carcinoma.},
journal = {Journal of cancer research and clinical oncology},
volume = {149},
number = {7},
issn = {0171-5216},
address = {Berlin},
publisher = {Springer},
reportid = {DKFZ-2022-01793},
pages = {3623-3635},
year = {2023},
note = {2023 Jul;149(7):3623-3635},
abstract = {Strategies for Indolamine-2,3-dioxygenase 1 (IDO1)
inhibition in cancer immunotherapy once produced encouraging
results, but failed in clinical trials. Recent evidence
indicates that immune cells in the tumour microenvironment,
especially macrophages, contribute to immune dysregulation
and therefore might play a critical role in drug
resistance.In this study, we investigated the significance
of IDO1 expressing immune cells in primary tumours and
corresponding lymph node metastases (LNMs) in oral squamous
cell carcinoma (OSCC) by immunohistochemistry. The link
between IDO1 and macrophages was investigated by flow
cytometry in tumour tissue, healthy adjacent tissue and
peripheral blood mononuclear cells (PBMCs). IDO1 activity
(measured as Kynurenine/Tryptophan ratio) was assessed by
ELISAs.High IDO1 expression in tumour-infiltrating immune
cells was significantly correlated with advanced stages
[Spearman's rank correlation (SRC), p = 0.027] and reduced
progression-free survival (multivariate Cox regression, p =
0.034). IDO1 was significantly higher expressed in PBMCs of
patients in advanced stages than in healthy controls (ANOVA,
p < 0.05) and IDO1+ macrophages were more abundant in
intratumoural areas than peritumoural (t test, p < 0.001).
IDO1 expression in PBMCs was significantly correlated with
IDO1 activity in serum (SRC, p < 0.05). IDO1 activity was
significantly higher in patients with LNMs (t test, p <
0.01).All in all, IDO1 expressing immune cells, especially
macrophages, are more abundant in advanced stages of OSCC
and are associated with reduced progression-free survival.
Further investigations are needed to explore their role in
local and systemic immune response. The IDO1 activity might
be a suitable biomarker of metastasis in OSCC patients.},
keywords = {IDO (Other) / Immunotherapy (Other) / Macrophage (Other) /
Oral squamous cell carcinoma (OSCC) (Other) / Tumour
microenvironment (Other)},
cin = {E221},
ddc = {610},
cid = {I:(DE-He78)E221-20160331},
pnm = {315 - Bildgebung und Radioonkologie (POF4-315)},
pid = {G:(DE-HGF)POF4-315},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35963900},
doi = {10.1007/s00432-022-04277-7},
url = {https://inrepo02.dkfz.de/record/181140},
}