Tumor immune microenvironment alterations using induction cetuximab in a phase II trial of deintensified therapy for p16-positive oropharynx cancer.

Background: We sought to characterize early changes in CD8 ⁺ tumor-infiltrating lymphocytes and tumor transcriptomes after induction cetuximab in a cohort with p16-positive oropharyngeal cancer on a phase II clinical de-escalation trial.
Methods: Tumor biopsies were obtained before and 1 week after a single cetuximab loading dose in eight patients enrolled in a phase II trial of cetuximab and radiotherapy. Changes in CD8 ⁺ tumor-infiltrating lymphocytes and transcriptomes were assessed.
Results: One week after cetuximab, five patients (62.5%) had an increase in CD8 ⁺ cell infiltration with a median (range) fold change of +5.8 (2.5-15.8). Three (37.5%) had unchanged CD8 ⁺ cells (median [range] fold change of -0.85 [0.8-1.1]). In two patients with evaluable RNA, cetuximab induced rapid tumor transcriptome changes in cellular type 1 interferon signaling and keratinization pathways.
Conclusions: Within 1 week, cetuximab induced measurable changes in pro-cytotoxic T-cell signaling and immune content.
(© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)