Imiquimod enhances anti-tumor effects of CD47 targeting in oral squamous cell carcinoma

  • Inflamm Res. 2026 Apr 17;75(1):93. doi: 10.1007/s00011-026-02226-5.
Hongzhi He  1  2 ,  Yu Hao  1  2  3 ,  Jing Chen  1  2 ,  Biao Ren  1 ,  Xin Zheng  1  2 ,  Xu Cao  4 ,  Bolei Li  5  6 ,  Lei Cheng  7  8
Affiliations
  • 1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 2. Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 3. Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 4. Shanghai Frontiers Science Center for Drug Target Identification and Delivery, and the Engineering Research Center of Cell and Therapeutic Antibody of the Ministry of Education, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China.
  • 5. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. [email protected].
  • 6. Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. [email protected].
  • 7. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. [email protected].
  • 8. Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. [email protected].
PMID: 41998354 DOI: 10.1007/s00011-026-02226-5
Abstract

Objectives: Regarding the limited clinical curative efficacy of CD47-targeted immunotherapy in treating oral squamous cell carcinoma (OSCC), the project aims to study the effect and mechanism of imiquimod-enhanced CD47 targeting in treating OSCC.

Methods: The effect of imiquimod on enhancing the phagocytosis and clearance of OSCC cells of CD47 targeting was studied through phagocytosis experiments and cell clearance experiments. Then, the safety of the local application of imiquimod was confirmed, and the effect of imiquimod was verified in vivo by immunohistochemistry staining and tumor growth analysis. Finally, transcriptome Sequencing, macrophage polarization, phagocytosis experiments, and cell clearance experiments were used to study the mechanism of imiquimod-enhanced CD47 targeting for treating OSCC.

Results: Imiquimod significantly enhances the phagocytosis and removal of OSCC cells when combined with CD47 targeting. In vivo studies have confirmed its capacity to potentiate CD47 targeting and revealed good biosafety of imiquimod. Mechanistically, imiquimod promotes M1 macrophage polarization by activating the Toll-like Receptor (TLR)7-nuclear factor (NF)-κB pathway in macrophages. This activation enhanced the phagocytic capacity of macrophages to effectively remove OSCC cells.

Conclusions: Imiquimod enhances CD47 targeting in phagocytosing and removing OSCC cells by activating macrophage TLR7-NF-κB activation and subsequent M1 polarization, providing a promising approach for treating OSCC.

Keywords
Imiquimod; Immunotherapy; Macrophages; NF-kappa B; Phagocytosis; Squamous cell carcinoma.
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