Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal forms of pancreatic cancer. This is due to its high rate of spread to other organs and resistance to immunotherapy. Although it is considered an immunologically ‘cold’ tumor, many immune cells are involved, some that help fight the tumor and others that actually support its growth. Current treatment strategies focus on blocking the activity of harmful cells while boosting the potential of beneficial ones. An effective anti-tumor response is a complex series of events in which immune cells migrate between tumors and draining lymph nodes to communicate and initiate an anti-tumor response. In this study, we used a new technique to track and label individual immune cells in mouse tumors and draining lymph nodes within a preclinical setup. We found that beneficial immune cells exit the tumor and migrate to the draining lymph nodes. Some of these cells could stimulate T cells to better kill the tumor, and others may serve as stem-like cells that can rejuvenate the anti-tumor T cell response. Importantly, the type of immune cells that leave the tumor changes with the stage of tumor progression. These new findings could lead to novel stage-specific immunotherapeutic strategies to boost the immune response in PDAC and enhance tumor clearance. Future studies would analyze available patient samples to translate our findings and inform clinicians about new targets for immunotherapy.