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

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

Joshua D Smith  1 , Megan L Ludwig  1 , Apurva D Bhangale  1 , Collin Brummel  1 , Paul L Swiecicki  2   3 , Francis P Worden  2   3 , Steven B Chinn  1   3 , Chaz L Stucken  1 , Andrew J Rosko  1   3 , Mark E P Prince  1   3 , Kelly M Malloy  1   3 , Keith A Casper  1   3 , Carol R Bradford  1   3 , Douglas B Chepeha  1   3 , Jennifer Shah  3   4 , Caitlin A Schonewolf  3   4 , Jonathon B McHugh  3   5 , Mukesh K Nyati  3   4 , Avraham Eisbruch  3   4 , Michelle L Mierzwa  3   4 , Matthew E Spector  1   3 , J Chad Brenner  1   3
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Free article
Clinical Trial

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

Joshua D Smith et al. Head Neck. 2023 May.
Free article

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.

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References

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