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Journal of Cancer Research and Clinical Oncology

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Open Access 13-08-2022 | Research

IDO1 is highly expressed in macrophages of patients in advanced tumour stages of oral squamous cell carcinoma

Authors: Ann-Kristin Struckmeier, Anne Radermacher, Michael Fehrenz, Tamara Bellin, Dalia Alansary, Philipp Wartenberg, Ulrich Boehm, Mathias Wagner, Anja Scheller, Jochen Hess, Julius Moratin, Christian Freudlsperger, Jürgen Hoffmann, Lorenz Thurner, Klaus Roemer, Kolja Freier, Dominik Horn

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2023

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusion

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.

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Title: IDO1 is highly expressed in macrophages of patients in advanced tumour stages of oral squamous cell carcinoma
Authors: Ann-Kristin Struckmeier
Anne Radermacher
Michael Fehrenz
Tamara Bellin
Dalia Alansary
Philipp Wartenberg
Ulrich Boehm
Mathias Wagner
Anja Scheller
Jochen Hess
Julius Moratin
Christian Freudlsperger
Jürgen Hoffmann
Lorenz Thurner
Klaus Roemer
Kolja Freier
Dominik Horn
Publication date: 13-08-2022
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 7/2023
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-022-04277-7

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