The immunotherapeutic role of indoleamine 2,3-dioxygenase (IDO) in head and neck squamous cell carcinoma: a systematic review.

ABSTRACT NUMBER: NESS_3

AUTHORS
Daniel J Lin1,2, James CK Ng2, Lei Huang1, Max Robinson3, James O’Hara2, Janet A Wilson2,4, Andrew L Mellor1

AFFILIATIONS
1. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
2. ENT Department, Freeman Hospital, Newcastle upon Tyne, UK
3. Centre for Oral Health Research, Newcastle University, Newcastle upon Tyne, UK
4. Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK

CORRESPONDING AUTHOR CONTACT EMAIL
ku.ca.eltsacwen@nil.leinad

MAIN ABSTRACT TEXT

Introduction
Novel cancer immunotherapy seeks to harness the body’s own immune system and tip the balance in favour of antitumour activity. The intracellular enzyme IDO is a critical regulator of the tumour microenvironment (TME) via tryptophan metabolism. The immune checkpoint, IDO1, breaks down tryptophan into its metabolites which results in TME immunosuppression. We aim to assess the evidence on IDO in head and neck squamous cell carcinoma (HNSCC).

Methods
A systematic review of literature and clinical trials databases.

Results
We included 32 studies. Of those, 5 involved cell lines, 7 assessed tumour immunohistochemistry, 6 measured IDO gene transcription, and 14 reported on clinical trials. IDO expression and activation by the Stimulator of Interferon Genes (STING) pathway played a central role in the human cell lines studied (SCC4, SCC15 and SCC25). Retrospective immunohistochemistry studies of lip, oral cavity, tonsil and larynx found that relatively high IDO expression correlated with worse survival1-3. Gene transcription studies showed increased IDO in tumours that expressed programmed death-ligand 1 (PD-L1) and harboured human papillomavirus (HPV). Phase I/II clinical trials showed 1) overall responses (34%) and disease control rates (62%) for IDO1 inhibitor in combination therapy, 2) consistent safety profile and 3) IDO gene expression as a predictive biomarker for response to therapy.

Conclusions
Retrospective studies of IDO presence in the TME suggests a link to HNSCC treatment outcome. However, IDO-driven immune modulation in the TME remains unclear. We now require prospective longitudinal studies on IDO activity and expression throughout treatment, thence optimise IDO-based immunotherapy.