Immunology Program Summary The overarching theme of the Immunology (IMM) Program is to define the basic mechanisms that control the function and regulation of immunity so that immunotherapies that generate specific and durable antitumor immune responses can be developed and optimized. Our Aims align with the Masonic Cancer Center (MCC) Strategic Plan pillars of driving research discoveries and accelerating the path to cures: 1) Identify basic mechanisms of immune cell regulation and function in the context of cancer and other chronic disease states that form the foundation for immune-mediated clinical interventions. 2) Develop, implement, and optimize cancer immunotherapies for clinical application. Yoji Shimizu, PhD, and Jeffrey Miller, MD, co-lead the IMM Program. Dr. Shimizu's expertise is in basic immunology and Dr. Miller's is in translational immunology; these synergize to accelerate the development and optimization of cancer immunotherapies to realize the full potential of immunotherapy for cancer patients. The IMM Program has 29 members, representing 11 departments and 3 schools or colleges. For the last budget year, these members were supported by $13.1 million in cancer-relevant research funding (direct costs), of which $1.85 million was from the National Cancer Institute. The Program's scientific accomplishments over the past 5 years include new insights into resident memory T cells and the development of a novel cancer clinical immunotherapy that targets them, the optimization and clinical testing of trispecific engagers that specifically activate NK cells, an expanding NCI-funded program focused on developing approaches to overcome the resistance of pancreatic cancer to immunotherapy by targeting both T cells and myeloid cells, a preclinical mouse model to address the mechanism that leads to neurotoxicity during CAR T cell therapy, and multiple approaches for optimizing and enhancing current cancer immunotherapies. Since 2018, Program members have published 349 papers, 24% of which resulted from intraprogrammatic collaborations, 35% from interprogrammatic collaborations, and 57% from external collaborations. MCC adds substantial value, such as the Cancer Research Translational Initiative, which allows IMM Program members to continue to move fundamental, high-impact scientific discoveries directly into cancer models and then on to clinical application. Program members also make extensive use of MCC Shared Resources and actively participate in Translational Working Groups. MCC-supported Program meetings and events foster our basic research and translational activities, and Program members are actively involved in community outreach and engagement activities, particularly those that focus on education and clinical trial enrollment.