Tumor immune microenvironment alterations using induction cetuximab in a phase <scp>II</scp> trial of deintensified therapy for <scp>p16‐positive</scp> oropharynx cancer
Joshua D. Smith, Megan Ludwig, Apurva D. Bhangale, Collin Brummel, Paul Swiecicki, Francis P. Worden, Steven B. Chinn, Chaz L. Stucken, Andrew J. Rosko, Mark E. Prince, Kelly M. Malloy, Keith Casper, Carol R. Bradford, Douglas B. Chepeha, Jennifer Shah, Caitlin A. Schonewolf, Jonathon B. McHugh, Mukesh K. Nyati, Avraham Eisbruch, Michelle Mierzwa, Matthew E. Spector, J. Chad Brenner
Abstract
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.