Funded by the Wine Celebration
Cancer treatments often fail to produce durable responses and resistant tumors eventually regrow. This process presents a major clinical challenge and results in significant patient mortality. The molecular details of this process, termed acquired resistance, are poorly understood and there are currently no therapeutic options to prevent it. For cancer immunotherapy, acquired resistance is emerging as a prevalent phenomenon affecting approximately half of patients who initially respond to treatment. Key to this process are the leftover tumor cells which remain alive and seed resistant tumors. We have observed a small subpopulation of cancer cells which survive direct cytotoxic T cell attack over prolonged time periods. These cells, termed persister cells, survive through unknown mechanisms. In this proposal we will determine how persister cells survive despite undergoing T cell attack and also how a subset of persister cells eventually regrow and exhibit overt T cell resistance. If successful, our proposed work will shed light on acquired resistance to immunotherapy and may reveal new approaches to prevent tumors from recurring.