Indoleamine 2,3-dioxygenase 2 immunohistochemical expression in a resected non-small cell lung cancer series

Background & Objectives: Indoleamine 2,3-dioxygenase 1 and 2 (IDO1 and IDO-2) are both implicated in immunomodulatory functions. Although several studies exist on the role of IDO-1 in human tissues, little is still known about IDO-2 functions and particularly about its involvement in non-small cell lung cancer (NSCLC) immunescape. 1,2 Methods: IDO-2 immunohistochemical expression was evaluated on 193 formalin-fixed and paraffin-embedded resected NSCLC, both in neoplastic cells and in normal adjacent lung parenchyma. Correlations with clinical-pathological data, tumour-infiltrating lymphocytes (TILs), IDO1, programmed cell death ligand-1 (PD-L1) and patients’ prognosis were analysed. Results: IDO-2 was chiefly enlightened at the interface between tumoural cells and tumoural stroma and at cell to cell junction; almost always normal bronchial epithelium expressed IDO-2. Moreover, IDO-2 overexpression is closely related both to high PD-L1 among squamous cell carcinomas (p=0.012) and to adenocarcinoma histotype (p<0.001). Considerably, IDO-2 overexpression correlates with a worse NSCLC prognosis (p=0.027), particularly in case of concurrent overexpression of IDO-1 (p=0.030) or high density of TILs (p=0.045), regardless of histotype. Conclusion: Our preliminary results have improved the knowledge about IDO-2 in lung tissue and NSCLC, suggesting a function both in immune system modulation and in tumoural invasiveness. The abovementioned interactions of IDO-2 with other microenvironmental molecules and their relationship with patients’ prognosis could support both the assessment of their status on pathological report and the introduction of combined immunotherapies as clinically useful. Nevertheless, further studies are needed to better understand IDO-2 role as potential biomarker in NSCLC.