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Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin

(2009) JOURNAL OF INVESTIGATIVE DERMATOLOGY. 129(11). p.2676-2685
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Abstract
Abstract: 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. PMID: 19516264 [PubMed - indexed for MEDLINE]
Keywords
DENDRITIC CELLS, TOPICAL IMIQUIMOD, ACTINIC KERATOSES, CYTOKINE PRODUCTION, TRANSPLANT RECIPIENTS, BOWENS-DISEASE, IMMUNE-RESPONSE, 5-PERCENT CREAM, TOLL-LIKE RECEPTOR-7, PLACEBO-CONTROLLED TRIAL

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  • Imiquimod enhances IFN-gamma production dr. Ilse Mollet
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MLA
Huang, SJ et al. “Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin.” JOURNAL OF INVESTIGATIVE DERMATOLOGY 129.11 (2009): 2676–2685. Print.
APA
Huang, SJ, Hijnen, D., Murphy, G., Kupper, T., Calarese, A., MOLLET, I., Schanbacher, C., et al. (2009). Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 129(11), 2676–2685.
Chicago author-date
Huang, SJ, D Hijnen, GF Murphy, TS Kupper, AW Calarese, ILSE MOLLET, CF Schanbacher, DM Miller, CD Schmults, and RA Clark. 2009. “Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin.” Journal of Investigative Dermatology 129 (11): 2676–2685.
Chicago author-date (all authors)
Huang, SJ, D Hijnen, GF Murphy, TS Kupper, AW Calarese, ILSE MOLLET, CF Schanbacher, DM Miller, CD Schmults, and RA Clark. 2009. “Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin.” Journal of Investigative Dermatology 129 (11): 2676–2685.
Vancouver
1.
Huang S, Hijnen D, Murphy G, Kupper T, Calarese A, MOLLET I, et al. Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin. JOURNAL OF INVESTIGATIVE DERMATOLOGY. NEW YORK: NATURE PUBLISHING GROUP; 2009;129(11):2676–85.
IEEE
[1]
S. Huang et al., “Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin,” JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 129, no. 11, pp. 2676–2685, 2009.
@article{877101,
  abstract     = {Abstract:
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.

PMID: 19516264 [PubMed - indexed for MEDLINE]},
  author       = {Huang, SJ and Hijnen, D and Murphy, GF and Kupper, TS and Calarese, AW and MOLLET, ILSE and Schanbacher, CF and Miller, DM and Schmults, CD and Clark, RA},
  issn         = {0022-202X},
  journal      = {JOURNAL OF INVESTIGATIVE DERMATOLOGY},
  keywords     = {DENDRITIC CELLS,TOPICAL IMIQUIMOD,ACTINIC KERATOSES,CYTOKINE PRODUCTION,TRANSPLANT RECIPIENTS,BOWENS-DISEASE,IMMUNE-RESPONSE,5-PERCENT CREAM,TOLL-LIKE RECEPTOR-7,PLACEBO-CONTROLLED TRIAL},
  language     = {eng},
  number       = {11},
  pages        = {2676--2685},
  publisher    = {NATURE PUBLISHING GROUP},
  title        = {Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin},
  url          = {http://dx.doi.org/10.1038/jid.2009.151},
  volume       = {129},
  year         = {2009},
}

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