Interrogating the tumor microenvironment (TME) in patients (pts) with head and neck mucosal squamous cell carcinoma (HNmSCC) treated with programmed death-1 (PD-1) inhibitors.

6048 Background: Survival in recurrent/metastatic HNmSCC remain poor. PD-1 inhibitors have become standard of care, demonstrating improved overall survival and toxicity when compared to chemotherapy and targeted therapy. Biomarkers such as PD-Ligand(L)1 combined proportion score (CPS) remain rudimentary, with CPS >20 showing a response rate of only 23% to pembrolizumab (KEYNOTE-048). We used high-dimensional imaging mass cytometry (IMC) to explore predictive biomarkers in HNmSCC pts receiving PD-1 inhibitor-based therapy. Methods: We retrospectively analysed 27 formalin-fixed paraffin embedded tissue samples from 24 pts prior to receiving PD-1 inhibitor-based therapy between May 2016 – April 2021. Clinicopathological characteristics including PD-L1, p16 status, prior treatment and survival data were collected. Pts were classified into responders (RES, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 complete response (CR) or partial response (PR), stable disease (SD) >6 months (mths)) and non-responders (non-RES, RECIST SD 6 mths, n = 4) and 14 pts were non-RES (RECIST SD 20% (n = 3) had a progression free survival of 80.3 mths, 26.8 mths and NE (unrelated death at 15.6 mths). Conclusions: The findings of this study identify mechanisms of PD-1 inhibitor response and resistance in HNmSCC pts, providing a unique opportunity to guide combination strategies and improve outcome.