Enhancing Immunotherapy by Targeting the Cancer Stem Cell Niche

Immunotherapy is the new promise in effectively combating cancer.  It has proven to be effective in solid tumors of an inflamed phenotype but still faces challenges in tumors that are less invaded by immune cells.  Cancer stem/initiating cells (CSCs) are defined as tumor cells that have the principal properties of self-renewal, clonal tumor initiation capacity, and clonal long-term repopulation potential.  According to the CSC paradigm, only complete eradication of these CSCs will prevent cancer from recurring.  CSCs reside in niches, which are anatomically distinct regions within the tumor microenvironment.  These niches maintain the principle properties of CSCs, preserve their phenotypic plasticity, protect them from the immune system, and facilitate their metastatic potential.  By combining methods of mouse genetics, human and mouse 3D primary organotypic cultures, biomedical live imaging and high throughput analyses on the single cell level, my research aims at understanding how immune cells and cancer stem cells interact within the niche during breast cancer evolution and metastasis.  Subsequently, we explore ways by which engineering the CSC niche will render it more susceptible to immunotherapy.