Prognostic impact of indoleamine 2,3-dioxygenase 1 (IDO1) mRNA expression on circulating tumour cells of patients with head and neck squamous cell carcinoma

Abstract

BackgroundWe sought to determine the prognostic role of indoleamine 2,3-dioxygenase 1 (IDO1) by evaluating IDO1 expression in circulating tumour cells (CTCs) at baseline and after completion of chemoradiotherapy in patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) treated with curative intent.MethodsIn a prospective cohort of 113 patients with LA HNSCC, we evaluated expression of IDO1 in the EpCAM+ CTC fraction at baseline and after cisplatin chemoradiation. The prognostic value of combined programmed cell death ligand-1 (PDL-1) and IDO1 expression was assessed.ResultsIDO1 was significantly overexpressed at baseline compared with the post-treatment counterparts (p=0.007). IDO1 messenger RNA (mRNA) expression at baseline was associated with better survival in terms of progression-free survival (PFS) (HR=0.19, p=0.017). Post-treatment IDO1 mRNA levels were correlated with unfavourable prognosis in terms of overall survival (OS) (HR=3.27, p=0.008). Patients with combined decreased expression levels of PDL-1 and IDO1 after treatment exhibited superior PFS (p=0.043) and OS (p=0.021).ConclusionsOur results strongly suggest that IDO1 mRNA expression is an independent prognostic factor for clinical outcome. Our study provides useful information for future trials combining chemoradiation with immune checkpoint inhibitors and IDO1 inhibitors.

The immunotherapeutic role of indoleamine 2,3‐dioxygenase in head and neck squamous cell carcinoma: A systematic review

“…Measuring expression during treatment, a significant (3.6‐fold) increase was seen in IDO expressed in PBMCs during radiotherapy for patients with stage III‐IV HNSCC 45 . Whereas after chemoradiation treatment, IDO1 mRNA levels correlated with worse overall survival, and a combined decrease in expression of PD‐L1 and IDO1 post‐treatment was associated with better progression‐free and overall survival 46 …”

“… 45 Whereas after chemoradiation treatment, IDO1 mRNA levels correlated with worse overall survival, and a combined decrease in expression of PD‐L1 and IDO1 post‐treatment was associated with better progression‐free and overall survival. 46 …”

Tumor Microenvironment and Immunotherapy Response in Head and Neck Cancer

“…First, MDSCs have the capacity to promote immunosuppression through IDO1 expression [ 151 ]. In HNSCC, high IDO1 expression has been correlated with worse outcomes in retrospective studies [ 152 , 153 ]. In the phase I/II ECHO-202/Keynote 037 study, which combined the IDO1 inhibitor epacadostat with pembrolizumab, among 2 patients with HNSCC who were included, one patient had stable disease as best response [ 154 ].…”

Circulating Tumour Cell Expression of Immune Markers as Prognostic and Therapeutic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

“…Assessing the correlation of CTC detection rate and disease stage between studies was not possible. In the two papers including locally advanced HNSCC patients, actual figures of "epithelial CTC positive" patients were not reported [18,22]. In these papers an EpCAM positive enrichment strategy was assumed to capture all epithelial expressing CTCs and gene expression values of this pooled cell group were normalised against a control value to assess overexpression of the target gene.…”

“…However, they did not state the HPV status of the entire cohort or correlate this to clinical outcome variables. The three remaining studies did not discuss HPV status [20][21][22].…”