Michelle M. Williams, PhD

The FDA approval of immunotherapies for metastatic triple-negative breast cancer suggests that stimulating an anti-tumor immune response may be an effective way to limit metastatic progression. These immunotherapies reactivate cytotoxic T cells, an immune cell type that is suppressed during tumor progression and cannot effectively target and kill tumor cells. However, liver metastases from several different tumor types have the poorest response to immunotherapy, possibly because liver metastases express the lowest levels of the molecules (PD-L1) and cells (T cells) that these immunotherapies target. Little is known about what regulates this site-specific therapy resistance in liver metastases. One strategy to increase response rates in metastatic breast cancer is to enhance our understanding of the interactions between metastatic breast cancer cells and the liver microenvironment. The goal of my research program is to address these gaps in knowledge and identify rational approaches to induce an anti-tumor immune response at this deadly metastatic site.
Current studies in the lab focus on the impact of tumor cell heme metabolism on the liver metastatic microenvironment by addressing the questions:

• Does tumor cell heme metabolism support progression and treatment resistance in breast cancer liver metastases by promoting suppressive T cell activity?
• Is the function of tissue resident immune cells, particularly liver resident macrophages or Kupffer cells, impacted by tumor cell secreted heme metabolites?
• Can heme metabolism alter the global metabolic profile of breast cancer cells to support survival in the glycolytically active liver?

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