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.
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.
Authors: Osama E Rahma; Ed Ashtar; Malgorzata Czystowska; Marta E Szajnik; Eva Wieckowski; Sarah Bernstein; Vincent E Herrin; Mortada A Shams; Seth M Steinberg; Maria Merino; William Gooding; Carmen Visus; Albert B Deleo; Judith K Wolf; Jeffrey G Bell; Jay A Berzofsky; Theresa L Whiteside; Samir N Khleif Journal: Cancer Immunol Immunother Date: 2011-09-17 Impact factor: 6.968
Authors: Frank Martiniuk; Diona L Damian; John F Thompson; Richard A Scolyer; Kam-Meng Tchou-Wong; William R Levis Journal: J Drugs Dermatol Date: 2010-11 Impact factor: 2.114