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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1530262
This article is part of the Research Topic Overcoming Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma View all 4 articles

Pilot Clinical Trial of Neoadjuvant Toll-like Receptor 7 Agonist (Imiquimod) Immunotherapy in Early-Stage Oral Squamous Cell Carcinoma

Provisionally accepted
Angela J. Yoon Angela J. Yoon 1*Richard Carvajal Richard Carvajal 2Evan Graboyes Evan Graboyes 1John M Kaczmar John M Kaczmar 1William G Albergotti William G Albergotti 1Alexandra E Kejner Alexandra E Kejner 1Scott H Troob Scott H Troob 3Elizabeth Philipone Elizabeth Philipone 3Jean-Sebastien Anoma Jean-Sebastien Anoma 1Kent E Armeson Kent E Armeson 1Elizabeth G Hill Elizabeth G Hill 1Mary S Richardson Mary S Richardson 1Tina Woods Tina Woods 1Bhisham Chera Bhisham Chera 1Farzad Nourollah-Zadeh Farzad Nourollah-Zadeh 1Byung J Lee Byung J Lee 1Subramanya N Pandruvada Subramanya N Pandruvada 1Antonis Kourtidis Antonis Kourtidis 1Christina Kingsley Christina Kingsley 1Elizabeth C O'quinn Elizabeth C O'quinn 1Stephanie Mills Stephanie Mills 1Victoria C Jordan Victoria C Jordan 1Mike Spencer Mike Spencer 4Danielle Fails Danielle Fails 4Trevor D Mckee Trevor D Mckee 5Mark Zaidi Mark Zaidi 5Alan Brisendine Alan Brisendine 1Shane Horn Shane Horn 1SHIKHAR MEHROTRA SHIKHAR MEHROTRA 1Besim Ogretmen Besim Ogretmen 1Jason G Newman Jason G Newman 1
  • 1 Medical University of South Carolina, Charleston, United States
  • 2 Institute of Cancer, Northwell Health, Lake Success, New York, United States
  • 3 Columbia University Irving Medical Center, Columbia University, New York, New York, United States
  • 4 Fortis Life Sciences, Montgomery, United States
  • 5 Pathomics Inc, Toronto, Canada

The final, formatted version of the article will be published soon.

    This study is being submitted to the Cancer Immunity and Immunotherapy section of Frontiers in Immunology. We performed an open-label, single-agent pilot study to evaluate neoadjuvant imiquimod immunotherapy's antitumor activity and safety in patients with early-stage oral squamous cell carcinoma. We also assessed a shift in the tumor microenvironment immune profile, PD-L1 expression-based biomarker, and one-year recurrence-free survival. We provide early evidence of the antitumor efficacy and safety of imiquimod. Overall, there was a reduction in clinical tumor size and evidence of immune-mediated antitumor pathologic responses. The adverse events of imiquimod therapy were mostly limited to application site mucositis. A significant increase in activated tumor-infiltrating lymphocytes and memory T-cells in the tumor microenvironment was noted after the therapy.

    Keywords: oral cancer, neoadjuvant clinical trial, toll-like 7 receptor agonist, imiquimod, immunotherapy Trial registration: ClinicalTrials.gov, Identifier NCT04883645

    Received: 18 Nov 2024; Accepted: 07 Jan 2025.

    Copyright: © 2025 Yoon, Carvajal, Graboyes, Kaczmar, Albergotti, Kejner, Troob, Philipone, Anoma, Armeson, Hill, Richardson, Woods, Chera, Nourollah-Zadeh, Lee, Pandruvada, Kourtidis, Kingsley, O'quinn, Mills, Jordan, Spencer, Fails, Mckee, Zaidi, Brisendine, Horn, MEHROTRA, Ogretmen and Newman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Angela J. Yoon, Medical University of South Carolina, Charleston, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.