ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1625867
This article is part of the Research TopicImmunology and Immunotherapy of Skin CancerView all 16 articles
Intratumoral Sustained Release of Resiquimod with Ablative Fractional Laser Induces Efficacy in a Cutaneous Squamous Cell Carcinoma Mouse Model
Provisionally accepted
Martin Wiinberg1*
Fredrik Melander1
Catharina M Lerche2
Thomas Lars Andresen3Uffe Høgh Olesen4Merete Haedersdal4- 1Technical University of Denmark, Kongens Lyngby, Denmark
- 2Department of Pharmcy, University of Copenhagen, Copenhagen, Denmark
- 3Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
- 4Department of Dermatology, Copenhagen University Hospital, Copenhagen, Denmark
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Introduction: The Toll-like receptor (TLR) 7/8 agonist resiquimod has shown promise for precancerous lesions of cutaneous squamous cell carcinoma (cSCC) but remains unexplored as a treatment for cSCC. Additionally, ablative fractional laser (AFL) has been shown to enhance the efficacy of TLR7 agonist in mouse tumor models. This study investigates the efficacy of intratumoral resiquimod formulated into a sustained-release gel (RSQ-gel) in a cSCC mouse model and compares RSQ-gel with topical imiquimod (IMQ) cream, a clinically approved TLR7 agonist. We further examine whether adjuvant AFL enhances the efficacy of RSQ-gel. Methods: A syngeneic transplanted cSCC mouse model was established using cells from a UVR-induced cSCC mouse model. The immunostimulatory effects of RSQ-gel were assessed by analyzing the expression of the activation marker CD86 on plasmacytoid dendritic cells (pDC) and cross-presenting conventional type I dendritic cells (XCR1+ cDC1) via flow cytometry. Tumor growth and survival outcomes were evaluated for RSQ-gel as monotherapy and in combination with AFL. Results: RSQ-gel was associated with activation of pDCs and XCR1+ cDC1s in the tumor-draining lymph node, as indicated by higher expression of CD86 compared to IMQ (P < 0.0001, P = 0.00175, respectively). RSQ-gel monotherapy delayed tumor growth but did not prolong survival (P = 0.0651). However, combining RSQ-gel with AFL resulted in prolonged survival compared to AFL-treated and untreated mice (P = 0.0153, P = 0.0214, respectively). Weekly RSQ-gel treatment induced comparable efficacy to daily topical IMQ treatment. Discussion: RSQ-gel with AFL demonstrated significant antitumor efficacy in the cSCC mouse model. Local RSQ-gel combined with adjuvant AFL may offer a promising therapeutic approach for cSCC.
Keywords: Drug Evaluation, Preclinical, Toll-like receptor agonists, Delayed-Action Preparations, Laser Therapy, Carcinoma, Squamous Cell
Received: 09 May 2025; Accepted: 22 Sep 2025.
Copyright: © 2025 Wiinberg, Melander, Lerche, Andresen, Olesen and Haedersdal. 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: Martin Wiinberg, martin.wiinberg95@gmail.com
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