Tumor-reactive T cells are often found in patients’ tumors, however, the tumors grow unimpeded; thus the T cells have been rendered dysfunctional. The overall goal of our laboratory is to understand how tumor-specific T cells become dysfunctional. We use genetically-engineered mouse models where we can track tumor-specific T cells as they differentiate in developing tumors and dissect the immunophenotypic, functional, transcriptional, and epigenetic properties of T cells using flow cytometry and next-generation sequencing. By unraveling the molecular pathways that lead to T cell dysfunction in cancer, we can devise new strategies for cancer immunotherapy.