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

Abstract

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.

Toll-like Receptor Agonists Are Unlikely to Provide Benefits in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

“…This study also evaluated pre-and post-treatment tumor samples for tumor immune infiltration and found that motolimod plus cetuximab was associated with a decreased induction of Tregs and enhanced CD8+ T cell infiltration of tumors following treatment. While this treatment-naïve group offers a better model for TLR-driven immune infiltration, this study was again limited by the lack of a control group as Cetuximab is associated with similar effects on the tumor-immune microenvironment [24]. Despite limitations of these studies, the mechanisms of TLR-agonist stimulation in clinical trials are unlikely to have relevance if they lack a treatment benefit.…”