Various studies have examined the association between serum vitamin D levels and different cancers; however, this is the first prospective study of this association with melanoma risk.,The aim of this study is to investigate the association between serum vitamin D [25(OH)D] levels and melanoma in a cohort of older, middle-aged Finnish male smokers.,We conducted a nested case-control study within the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study.,From the ATBC cohort, 368 subjects were chosen for our study; 92 participants that developed melanoma and 276 matched control subjects.,At study baseline, lifestyle questionnaires and blood samples were collected.,Serum 25(OH)D was modeled as three sets of categorical variables: clinically-defined categories, season-specific quartiles and season-adjusted residual quartiles.,Conditional logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs) to estimate the association between circulating vitamin D and melanoma risk.,Overall no association of serum 25(OH)D and melanoma risk was observed.,A decreased risk of developing melanoma was observed in the middle categories compared to the lowest category, albeit not significant.,Results indicate no association between serum 25(OH)D levels and melanoma.,Additional studies, including possibly consortium efforts, are needed to investigate the association between serum 25(OH)D levels and risk of melanoma in larger, more diverse study populations.
Immunotherapy with high-dose interleukin-2 (HDIL-2) is an effective treatment for patients with metastatic melanoma and renal cell carcinoma.,However, it is accompanied by severe toxicity involving endothelial cell injury and induction of vascular leak syndrome (VLS).,In this study, we found that resveratrol, a plant polyphenol with anti-inflammatory and anti-cancer properties, was able to prevent the endothelial cell injury and inhibit the development of VLS while improving the efficacy of HDIL-2 therapy in the killing of metastasized melanoma.,Specifically, C57BL/6 mice were injected with B16F10 cells followed by resveratrol by gavage the next day and continued treatment with resveratrol once a day.,On day 9, mice received HDIL-2.,On day 12, mice were evaluated for VLS and tumor metastasis.,We found that resveratrol significantly inhibited the development of VLS in lung and liver by protecting endothelial cell integrity and preventing endothelial cells from undergoing apoptosis.,The metastasis and growth of the tumor in lung were significantly inhibited by HDIL-2 and HDIL-2 + resveratrol treatment.,Notably, HDIL-2 + resveratrol co-treatment was more effective in inhibiting tumor metastasis and growth than HDIL-2 treatment alone.,We also analyzed the immune status of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSC) and FoxP3+CD4+ regulatory T cells (Treg).,We found that resveratrol induced expansion and suppressive function of MDSC which inhibited the development of VLS after adoptive transfer.,However, resveratrol suppressed the HDIL-2-induced expansion of Treg cells.,We also found that resveratrol enhanced the susceptibility of melanoma to the cytotoxicity of IL-2-activated killer cells, and induced the expression of the tumor suppressor gene FoxO1.,Our results suggested the potential use of resveratrol in HDIL-2 treatment against melanoma.,We also demonstrated, for the first time, that MDSC is the dominant suppressor cell than regulatory T cell in the development of VLS.