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Br J Dermatol. 2008 Sep;159(3):606-14. doi: 10.1111/j.1365-2133.2008.08709.x. Epub 2008 Jul 4.

Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes and restore the Th1/Th2 balance in patients with metastatic melanoma.

Author information

1
Department of Oncology, St George's University of London, London SW17 0RE, UK. deborahgreen@doctors.org.uk

Abstract

BACKGROUND:

Patients with metastatic skin disease in malignant melanoma are difficult to treat, with unresectable lesions proving the biggest challenge. We have recently published data showing a significant clinical response in patients with multiple in-transit melanoma metastases treated with a combination of topical imiquimod and intralesional interleukin (IL)-2. Here we report the results of immunological analysis with the aim of highlighting correlations with our clinical findings.

OBJECTIVES:

To investigate the systemic effects of our localized combination treatment in patients with accessible metastases of melanoma, and to correlate this with their clinical responses.

METHODS:

The peripheral blood mononuclear cells of patients were collected at various time points throughout the treatment. Using antibodies to T-cell subsets we measured the changes in cell populations, and along with polyclonal stimulation, changes in cytokine production from these cells over a treatment course.

RESULTS:

We report an increase in the mean CD4/CD8 ratio from 2.78 to 3.54 with treatment (P < 0.01), and a rise in the percentage of CD25+ cells in the CD4+ population from 14.52% to 38.56%. Furthermore, staining with activation and T-regulatory markers showed that the majority of this population is activated T cells. Cytokine analysis on polyclonally stimulated peripheral blood mononuclear cells showed an increase in the ability of cells to produce interferon (IFN)-gamma over the treatment course, with an initial rise in the IFN-gamma/IL-5 ratio in five of six patients.

CONCLUSIONS:

The results of this study provide evidence that, in the majority of patients with in-transit metastases of melanoma, therapy with a combination of topical imiquimod and intralesional IL-2 induces a systemic immunological effect by reversing some of changes noted in patients with malignant disease.

[Indexed for MEDLINE]

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