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Meghan J. O'Melia
BME Ph.D. Proposal Presentation
Date & Time: Monday, November 4, 2019 at 9:00am
Location: IBB 1128
Advisor:
Susan N. Thomas, PhD
Committee:
Ed Botchwey, PhD
Andres Garcia, PhD
Doug Graham, MD, PhD
Cheng Zhu, PhD
Title: Biomaterial techniques to evaluate and engineer the tumor immune microenvironment in breast cancer and melanoma
Abstract:
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 18% 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. In the proposed research, I will utilize sophisticated immunological characterization approaches and engineered biomaterial technologies applied to advanced preclinical tumor models to analyze and engineer the in vivo breast tumor and melanoma 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 that result in disease progression. We expect the following outcomes: 1) improved understanding of the tumor immune microenvironment throughout the development and progression of TNBC and melanoma; 2) novel models with which to analyze antigen sensing and model the breast tumor microenvironment; and 3) insight into optimal immunotherapeutic strategies for both TNBC and melanoma.
