Biomaterial techniques to evaluate and engineer the tumor immune microenvironment in breast cancer and melanoma

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O'Melia, Meghan
Thomas, Susan Napier
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Immunotherapy has emerged as the most promising new approach to increase cancer patient survival through its potential to treat both advanced disseminated disease and protect against recurrence. However, response rates in advanced melanoma and the most aggressive and deadliest type of breast cancer, triple-negative breast cancer (TNBC) are disappointingly low: only 20-40% and ~16% of patients, respectively, respond to immune checkpoint blockade (ICB) therapy. Despite immunotherapy’s potential in boosting anti-tumor immune response, tumor-induced immune suppression subverts both its development and effects. Overcoming tumor immune suppression, the mechanisms of which are still poorly understood, is thus a critical hurdle to improving the efficacy of immunotherapy in reducing the mortality associated with advanced melanoma and TNBC. Through this research, sophisticated immunological characterization approaches and engineered biomaterial techniques have been applied to preclinical tumor models to analyze and engineer the in vivo melanoma and breast tumor immune microenvironment. The central hypothesis of this work is that modeling immune suppression underlying melanoma and TNBC disease progression will reveal mechanisms of immunotherapeutic resistance to inform the development of improved immunotherapeutic strategies. The goal of this work is to utilize bioengineering approaches and techniques to manipulate and analyze immune suppressive mechanisms within the tumor microenvironment (TME) that result in disease progression. This has resulted in the following outcomes: 1) improved understanding of the tumor immune microenvironment throughout the development and progression of melanoma and TNBC; 2) novel models with which to analyze antigen (Ag) sensing and model the breast TME; and 3) insight into optimal immunotherapeutic strategies for both melanoma and TNBC.
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