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

Head Neck. 2023 May;45(5):1281-1287. doi: 10.1002/hed.27344. Epub 2023 Mar 18.

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.

Keywords: CD8; HPV; TILs; cetuximab; oropharynx.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Cetuximab / therapeutic use
  • Humans
  • Oropharyngeal Neoplasms* / pathology
  • Tumor Microenvironment

Substances

  • Cetuximab