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@ARTICLE{Hoffmann:282756,
author = {I. Hoffmann and M. P. Dragomir$^*$ and N. Monjé and C.
Keunecke and C. A. Kunze and S. Schallenberg and S.
Marchenko and W. D. Schmitt and H. Kulbe and J. Sehouli and
I. E. Braicu and P. Jank and C. Denkert and S. Darb-Esfahani
and D. Horst and B. V. Sinn and C. Sers and P. Bischoff$^*$
and E. T. Taube},
title = {{I}ncreased expression of {IDO}1 is associated with
improved survival and increased number of {TIL}s in patients
with high-grade serous ovarian cancer.},
journal = {Neoplasia},
volume = {44},
issn = {1522-8002},
address = {Basingstoke},
publisher = {Stockton Press},
reportid = {DKFZ-2023-01875},
pages = {100934},
year = {2023},
abstract = {The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) plays a
crucial role in regulating the immune system's response to
tumors, but its exact role in cancer, especially in
high-grade serous ovarian cancer (HGSOC), remains
controversial. We aimed to investigate the prognostic impact
of IDO1 expression and its correlation with
tumor-infiltrating lymphocytes (TILs) in
HGSOC.Immunohistochemical (IHC) staining and bioimage
analysis using the QuPath software were employed to assess
IDO1 protein expression in a well-characterized cohort of
507 patients with primary HGSOC. Statistical evaluation was
performed using SPSS, and in silico validation considering
IDO1 mRNA expression in bulk and single-cell gene expression
datasets was conducted. Additionally, IDO1 expression in
interferon-gamma (IFNG) stimulated HGSOC cell lines was
analyzed.Our findings revealed that IDO1 protein and mRNA
expression serve as positive prognostic markers for overall
survival (OS) and progression-free survival (PFS) in HGSOC.
High IDO1 expression was associated with a significant
improvement in OS by 21 months (p < 0.001) and PFS by 6
months (p = 0.016). Notably, elevated IDO1 expression
correlated with an increased number of CD3+ (p < 0.001),
CD4+ (p < 0.001), and CD8+ TILs (p < 0.001). Furthermore,
high IDO1 mRNA expression and protein level were found to be
associated with enhanced responsiveness to pro-inflammatory
cytokines, particularly IFNG.Our study provides evidence
that IDO1 expression serves as a positive prognostic marker
in HGSOC and is associated with an increased number of CD3+,
CD4+ and CD8+ TILs. Understanding the intricate relationship
between IDO1, TILs, and the tumor microenvironment may hold
the key to improving outcomes in HGSOC.},
keywords = {HGSOC (Other) / IDO1 (Other) / Ovarian cancer (Other) /
Prognostic marker (Other) / TILs (Other)},
cin = {BE01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37703626},
doi = {10.1016/j.neo.2023.100934},
url = {https://inrepo02.dkfz.de/record/282756},
}