TY  - JOUR
AU  - Struckmeier, Ann-Kristin
AU  - Radermacher, Anne
AU  - Fehrenz, Michael
AU  - Bellin, Tamara
AU  - Alansary, Dalia
AU  - Wartenberg, Philipp
AU  - Boehm, Ulrich
AU  - Wagner, Mathias
AU  - Scheller, Anja
AU  - Hess, Jochen
AU  - Moratin, Julius
AU  - Freudlsperger, Christian
AU  - Hoffmann, Jürgen
AU  - Thurner, Lorenz
AU  - Roemer, Klaus
AU  - Freier, Kolja
AU  - Horn, Dominik
TI  - IDO1 is highly expressed in macrophages of patients in advanced tumour stages of oral squamous cell carcinoma.
JO  - Journal of cancer research and clinical oncology
VL  - 149
IS  - 7
SN  - 0171-5216
CY  - Berlin
PB  - Springer
M1  - DKFZ-2022-01793
SP  - 3623-3635
PY  - 2023
N1  - 2023 Jul;149(7):3623-3635
AB  - 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.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.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).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.
KW  - IDO (Other)
KW  - Immunotherapy (Other)
KW  - Macrophage (Other)
KW  - Oral squamous cell carcinoma (OSCC) (Other)
KW  - Tumour microenvironment (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:35963900
DO  - DOI:10.1007/s00432-022-04277-7
UR  - https://inrepo02.dkfz.de/record/181140
ER  -