Coexpression patterns of IDO-1, PD-L1 and EGFR in non-small cell lung cancer

Abstract

Background: Indoleamine-2, 3-dioxygenase (IDO), a well-established immune suppressor, may offset efficacy of immune checkpoint inhibitors (ICIs) such as programmed death receptor ligand-1(PD-L1) by inducing unfavorable tumor microenvironment. The unpredictability of one ICI response may partially due to the concomitant presence of other ICIs. Therefore, increasing interest has been focus on the dual ICIs or the combination of ICIs with conventional treatment modalities such as radiotherapy, chemotherapy as well as target therapy. This study aimed to study the coexpression patterns and significance of IDO-1, PD-L1 and epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC). Methods: Patients with newly diagnosed NSCLC enrolled in three prospective surgery clinical trials were included in this study. The expressions of IDO-1, PD-L1 and EGFR were evaluated by immunohistochemistry (IHC). For positive cases, the percentile score and H-score were generated respectively from two independent pathologists. The descriptive analysis of Crosstab was used to compare the distributions of these biomarkers expression by pathological types. Results: A total of 117 patients (adenocarcinoma -54%, squamous cell carcinoma -32% and others -14%) with pretreatment tissue specimen available for IHC analysis were studied. Of these, 105 (90%) were from lung primary and 12 (10%) from distant metastasis sites. The expressions of IDO-1 (≥ 1%), PD-L1 ((≥ 1%) and EGFR (≥ 90% or intensity = 3) were identified in 43%, 40% and 52% of NSCLC patients. For IDO-1 and PD-L1, coexpression rates were 21% for co-positive and 37% for co-negative. However, there were still 42% patients showed isolated PD-L1 (20%) or IDO-1 expression (22%). The coexpression rates for EGFR and IDO-1 were 21% for co-positive and 26% for co-negative. The coexpression rates for EGFR and PD-L1 were 20% for co-positive and 25% for co-negative. 38% patients had a positive EGFR with either IDO-1 or PD-L1 positive. The expression patterns were not significant associated with clinical factors including pathological types and differentiation grades. Conclusions: IDO-1 and PD-L1 expression patterns may be useful in the selection of NSCLC patients for dual ICIs immunotherapy. The combinations of EGFR target therapy with immunotherapy may benefit some of NSCLC patients. However, testing expression status of EGFR and immune checkpoints becomes essential since majority of NSCLC patients exhibits EGFR positive with IDO-1 or PD-L1 negative patterns. © 2019 by American Society of Clinical Oncology