Journal Article

DKFZ-2023-01875

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Increased expression of IDO1 is associated with improved survival and increased number of TILs in patients with high-grade serous ovarian cancer.

Hoffmann, I. ; Dragomir, M. P.DKFZ* ; Monjé, N. ; Keunecke, C. ; Kunze, C. A. ; Schallenberg, S. ; Marchenko, S. ; Schmitt, W. D. ; Kulbe, H. ; Sehouli, J. ; Braicu, I. E. ; Jank, P. ; Denkert, C. ; Darb-Esfahani, S. ; Horst, D. ; Sinn, B. V. ; Sers, C. ; Bischoff, P.DKFZ* ; Taube, E. T.

2023
Stockton Press Basingstoke

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Please use a persistent id in citations: doi:10.1016/j.neo.2023.100934

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.

Keyword(s): HGSOC ; IDO1 ; Ovarian cancer ; Prognostic marker ; TILs

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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