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- W2891585172 abstract "Abstract Immunotherapeutic strategies in cancer rely upon tumor immunogenicity for their efficacy. However, the regulation of immune effector molecules in melanoma is poorly understood. High Dicer expression in melanoma correlates with more aggressive tumors and poor prognosis/patient survival. Dicer regulates gene expression through processing of microRNAs, but its potential role in regulating the immunogenicity of melanoma has not been described. Here, we demonstrate that Dicer suppresses MHC class I and II cell surface expression, as well as CD40 and PD-L1 in melanoma. By using a genetic approach wherein we challenged C57BL/6 mice with melanoma cells stably expressing Dicer shRNA, we showed that Dicer knockdown decreased tumor progression and extended overall survival. Interestingly, Dicer knockdown had no effect on melanoma cell proliferation or survival in vitro, suggesting that the delay in tumor growth may be due to an augmented immune response. Tumor control of Dicer knockdown melanoma cells was dependent upon an intact immune system, as revealed by studies using NSG mice. Mechanistically, this anti-tumor immune response was dependent upon CD8+ T cells. Subsequent studies demonstrated that melanoma Dicer expression was able to suppress CD8+ T cell killing in vitro. Taken together, this suggests a model wherein Dicer negatively regulates melanoma immunogenicity and protects against CD8+ T cell anti-tumor immunity. Using this insight, we may better stratify patients for immunotherapies such as checkpoint inhibition and cell-based vaccination strategies. Dicer also makes an attractive target for modulating baseline tumor cell immunogenicity, subsequently enhancing melanoma immunotherapy and patient survival." @default.
- W2891585172 created "2018-09-27" @default.
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- W2891585172 date "2016-05-01" @default.
- W2891585172 modified "2023-09-27" @default.
- W2891585172 title "Dicer regulates tumor immunogenicity in melanoma" @default.
- W2891585172 doi "https://doi.org/10.4049/jimmunol.196.supp.213.6" @default.
- W2891585172 hasPublicationYear "2016" @default.
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