Tumor micro-environment contributions to TNBC chemoresistance: Extracellular matrix & immune therapies
Extensive fibrotic desmoplasia is observed in residual TNBC tumors following chemotherapy treatment. As shown on the left, PDX residual tumors have infiltration of fibroblasts and deposition of various ECM components that is reverted as tumors relapse. Our goal is to elucidate the functional contributions of tumor cell-ECM interactions to survival and relapse of post-chemotherapy residual disease. Furthermore, we are investigating mechanisms of metabolic crosstalk between tumor and stroma cell populations. We are answering these questions using multi-spectral quantitative pathology imaging, tumor-stroma co-culture organoid models, genetic, and pharmacologic tools in PDX models and TNBC cell lines.
Based on expression of cell-surface antigens such as mucins (e.g. MUC1), we will assess the anti-tumor activity of multi-tumor antigen-specific T cells against treatment-naive and chemoresistant TNBC cells.