Increased expression of IDO1 is associated with improved survival and increased number of TILs in patients with high-grade serous ovarian cancer

Inga Hoffmann; Mihnea P. Dragomir; Nanna Monjé; Carlotta Keunecke; Catarina Alisa Kunze; Simon Schallenberg; Sofya Marchenko; Wolfgang D. Schmitt; Hagen Kulbe; Jalid Sehouli; Ioana Elena Braicu; Paul Jank; Carsten Denkert; Silvia Darb-Esfahani; David Horst; Bruno V. Sinn; Christine Sers; Philip Bischoff; Eliane T. Taube

Neoplasia: An International Journal for Oncology Research (Oct 2023)

Increased expression of IDO1 is associated with improved survival and increased number of TILs in patients with high-grade serous ovarian cancer

Inga Hoffmann,
Mihnea P. Dragomir,
Nanna Monjé,
Carlotta Keunecke,
Catarina Alisa Kunze,
Simon Schallenberg,
Sofya Marchenko,
Wolfgang D. Schmitt,
Hagen Kulbe,
Jalid Sehouli,
Ioana Elena Braicu,
Paul Jank,
Carsten Denkert,
Silvia Darb-Esfahani,
David Horst,
Bruno V. Sinn,
Christine Sers,
Philip Bischoff,
Eliane T. Taube

Affiliations

Inga Hoffmann: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Mihnea P. Dragomir: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Nanna Monjé: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Carlotta Keunecke: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Catarina Alisa Kunze: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Simon Schallenberg: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Sofya Marchenko: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Wolfgang D. Schmitt: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Hagen Kulbe: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Tumorbank Ovarian Cancer Network, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Jalid Sehouli: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Tumorbank Ovarian Cancer Network, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Ioana Elena Braicu: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Tumorbank Ovarian Cancer Network, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Paul Jank: Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Baldingerstraße, 35043 Marburg, Germany
Carsten Denkert: Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Baldingerstraße, 35043 Marburg, Germany
Silvia Darb-Esfahani: MVZ Pathologie Spandau, Stadtrandstr. 555, 13589 Berlin Spandau; MVZ Pathologie Berlin-Buch, Lindenberger Weg 27, Haus 207, 13125 Berlin
David Horst: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Bruno V. Sinn: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Christine Sers: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Philip Bischoff: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Eliane T. Taube: Institute of Pathology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; Corresponding author.

Journal volume & issue: Vol. 44
p. 100934

Abstract

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Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Published in Neoplasia: An International Journal for Oncology Research

ISSN: 1522-8002 (Print); 1476-5586 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/neoplasia/

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