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

• DOI: 10.1002/hed.27344
• Publication Date: 2023-03-18T10:08:34Z
• Authors: Joshua D. Smith; Megan L. Ludwig; Apurva D. Bhangale; Collin Brummel; Paul L. Swiecicki; Francis P. Worden; Steven B. Chinn; Chaz L. Stucken; Andrew J. Rosko; Mark E. P. Prince; Kelly M. Malloy; Keith A. Casper; Carol R. Bradford; Douglas B. Chepeha; Jennifer Shah; Caitlin A. Schone...; Jonathon B. McHugh; Mukesh K. Nyati; Avraham Eisbruch; Michelle L. Mierzwa; Matthew E. Spector; J. Chad Brenner
• Keywords: Oropharyngeal Neoplasms; Tumor Microenvironment; Humans; Cetuximab; CD8-Positive T-Lymphocytes; 3. Good health

AbstractBackgroundWe 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.MethodsTumor 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.ResultsOne 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.ConclusionsWithin 1 week, cetuximab induced measurable changes in pro‐cytotoxic T‐cell signaling and immune content.