%0 Journal Article
%A Hoffmann, Inga
%A Dragomir, Mihnea P
%A Monjé, Nanna
%A Keunecke, Carlotta
%A Kunze, Catarina Alisa
%A Schallenberg, Simon
%A Marchenko, Sofya
%A Schmitt, Wolfgang D
%A Kulbe, Hagen
%A Sehouli, Jalid
%A Braicu, Ioana Elena
%A Jank, Paul
%A Denkert, Carsten
%A Darb-Esfahani, Silvia
%A Horst, David
%A Sinn, Bruno V
%A Sers, Christine
%A Bischoff, Philip
%A Taube, Eliane T
%T Increased expression of IDO1 is associated with improved survival and increased number of TILs in patients with high-grade serous ovarian cancer.
%J Neoplasia
%V 44
%@ 1522-8002
%C Basingstoke
%I Stockton Press
%M DKFZ-2023-01875
%P 100934
%D 2023
%X 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.
%K HGSOC (Other)
%K IDO1 (Other)
%K Ovarian cancer (Other)
%K Prognostic marker (Other)
%K TILs (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37703626
%R 10.1016/j.neo.2023.100934
%U https://inrepo02.dkfz.de/record/282756