Imiquimod enhances IFN-gamma production and effector function of T cells infiltrating human squamous cell carcinomas of the skin

J Invest Dermatol. 2009 Nov;129(11):2676-85. doi: 10.1038/jid.2009.151. Epub 2009 Jun 11.


Squamous cell carcinomas (SCCs) are sun-induced skin cancers that are particularly numerous and aggressive in patients taking T-cell immunosuppressant medications. Imiquimod is a topical immune response modifier and Toll-like receptor 7 (TLR7) agonist that induces the immunological destruction of SCC and other skin cancers. TLR7 activation by imiquimod has pleiotropic effects on innate immune cells, but its effects on T cells remain largely uncharacterized. Because tumor destruction and formation of immunological memory are ultimately T-cell-mediated effects, we studied the effects of imiquimod therapy on effector T cells infiltrating human SCC. SCC treated with imiquimod before excision contained dense T-cell infiltrates associated with tumor cell apoptosis and histological evidence of tumor regression. Effector T cells from treated SCC produced more IFN-gamma, granzyme, and perforin and less IL-10 and transforming growth factor-beta (TGF-beta) than T cells from untreated tumors. Treatment of normal human skin with imiquimod induced activation of resident T cells and reduced IL-10 production but had no effect on IFN-gamma, perforin, or granzyme, suggesting that these latter effects arise from the recruitment of distinct populations of T cells into tumors. Thus, imiquimod stimulates tumor destruction by recruiting cutaneous effector T cells from blood and by inhibiting tonic anti-inflammatory signals within the tumor.

Publication types

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

MeSH terms

  • Aminoquinolines / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Biopsy
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Granzymes / metabolism
  • Humans
  • Imiquimod
  • In Vitro Techniques
  • Interferon-gamma / metabolism*
  • Interleukin-10 / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Perforin
  • Pore Forming Cytotoxic Proteins / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Transforming Growth Factor beta / metabolism


  • Aminoquinolines
  • Antineoplastic Agents
  • IL10 protein, human
  • PRF1 protein, human
  • Pore Forming Cytotoxic Proteins
  • Transforming Growth Factor beta
  • Perforin
  • Interleukin-10
  • Interferon-gamma
  • Granzymes
  • Imiquimod