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

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 signifcance 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 fow 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-infltrating immune cells was signifcantly 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 signifcantly 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 signifcantly correlated with IDO1 activity in serum (SRC, p<0.05). IDO1 activity was signifcantly 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.