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

Abstract

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. Tumor biopsies were obtained before and 1week 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. 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. Within 1week, cetuximab induced measurable changes in pro-cytotoxic T-cell signaling and immune content.