Targeting Extradomain-B Fibronectin to Monitor Immune Checkpoint Therapy with MRI in Head and Neck Squamous Cell Carcinoma

Motivation: Only 15-20% of patients with advanced head and neck squamous cell carcinoma (HNSCC) benefit from immunotherapy, with no reliable strategies to quickly predict or determine a patient’s response to treatment. Goal(s): We aim to evaluate a therapeutic monitoring strategy using MRI by targeting extradomain B fibronectin (EDB-FN) in the tumor stroma. Approach: Using mouse models bearing HNSCC allografts, we treated and monitored therapeutic efficacy of anti-PDL1 immunotherapy with MRI using MT218, our EDB-FN-targeted contrast agent. Results: Treatment-responsive tumors exhibited unique expression patterns of EDB-FN compared to controls that were visualized with MT218 MRI, demonstrating the potential for predicting and monitoring HNSCC immunotherapy response. Impact: We demonstrate that EDB-FN is a potential biomarker for immunotherapy response in HNSCC, and our MRI strategy targeting EDB-FN offers clinicians a potential method for predicting or monitoring immunotherapeutic outcomes to improve the clinical management of HNSCC.