769 AP736, a newly developed synthetic compound exerting whitening and anti-aging dual effect on skin cells

Abstract

Seoul-t'ukpyolsi, Republic of Korea Acral melanoma is of particular interest to understand melanoma pathogenesis, because it is invasive and treatment-resistant, but not associated with sun exposure. We studied gene expression profiles of human acral melanoma (n¼10) compared to non-acral melanoma (n¼21 for array, n¼5 for PCR), paired non-melanoma tissues of the melanoma patients (n¼11), and acral (n¼7) or non-acral (n¼12) healthy skin from volunteers by utilizing IHC, RT-PCR, and gene arrays. Hallmark melanoma genes (MLANA, MITF, PRAME, and MAGEA12) were equivalently enriched in both acral and non-acral melanoma compared to paired non-melanoma or normal skin. Keratinocyte proliferation marker (KRT16) was higher in acral melanoma compared to non-acral melanoma or normal skin. T cell and dendritic cell activation was high both in acral and non-acral melanoma based on expression of CD2, CD3, CD8, CD86, DC-LAMP, ITK, and JAK3 mRNAs; high interferon pathway activation was also detected. Importantly, a key molecular distinction was lower expression of negative immune regulatory genes (FoxP3, FAS, CTLA4, PD-1, PD-1 L1, PD-1 L2, IL-10, P53, CD69) in acral melanoma compared to non-acral melanoma. Gene set variation analysis also revealed lower regulatory T cell vs. conventional T cell signature in acral melanoma compared to non-acral melanoma. We thus hypothesize that negative immune regulators are less activated in the tumor microenvironment of acral melanoma, suggesting treatment-resistant mechanism of acral melanoma to immunotherapies targeting negative regulators of T cells.